AU2008261668C1 - A drug delivery system for the prevention of cerebral vasospasm - Google Patents
A drug delivery system for the prevention of cerebral vasospasm Download PDFInfo
- Publication number
- AU2008261668C1 AU2008261668C1 AU2008261668A AU2008261668A AU2008261668C1 AU 2008261668 C1 AU2008261668 C1 AU 2008261668C1 AU 2008261668 A AU2008261668 A AU 2008261668A AU 2008261668 A AU2008261668 A AU 2008261668A AU 2008261668 C1 AU2008261668 C1 AU 2008261668C1
- Authority
- AU
- Australia
- Prior art keywords
- calcium channel
- vasospasm
- cerebral
- therapeutic agent
- antagonist
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 208000001286 intracranial vasospasm Diseases 0.000 title claims abstract description 40
- 230000002265 prevention Effects 0.000 title abstract description 10
- 238000012377 drug delivery Methods 0.000 title description 5
- 206010047163 Vasospasm Diseases 0.000 claims abstract description 107
- 210000001627 cerebral artery Anatomy 0.000 claims abstract description 67
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 36
- 210000002330 subarachnoid space Anatomy 0.000 claims abstract description 34
- 230000000144 pharmacologic effect Effects 0.000 claims abstract description 21
- 239000003814 drug Substances 0.000 claims description 174
- 229940124597 therapeutic agent Drugs 0.000 claims description 112
- 229940127291 Calcium channel antagonist Drugs 0.000 claims description 111
- 150000001875 compounds Chemical class 0.000 claims description 103
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 claims description 96
- 239000000480 calcium channel blocker Substances 0.000 claims description 96
- 238000000034 method Methods 0.000 claims description 93
- 239000007787 solid Substances 0.000 claims description 85
- -1 bamidipine- Chemical compound 0.000 claims description 68
- 230000000694 effects Effects 0.000 claims description 65
- 239000002308 endothelin receptor antagonist Substances 0.000 claims description 63
- 239000000203 mixture Substances 0.000 claims description 58
- UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 claims description 46
- 229960000715 nimodipine Drugs 0.000 claims description 46
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 claims description 42
- 229960001783 nicardipine Drugs 0.000 claims description 42
- 238000002347 injection Methods 0.000 claims description 25
- 239000007924 injection Substances 0.000 claims description 25
- 230000001225 therapeutic effect Effects 0.000 claims description 25
- 229940118365 Endothelin receptor antagonist Drugs 0.000 claims description 15
- 230000002490 cerebral effect Effects 0.000 claims description 15
- 102000005962 receptors Human genes 0.000 claims description 15
- 108020003175 receptors Proteins 0.000 claims description 15
- 229940125968 Voltage-Gated Calcium Channel inhibitor Drugs 0.000 claims description 11
- 238000013268 sustained release Methods 0.000 claims description 11
- 239000012730 sustained-release form Substances 0.000 claims description 11
- 230000001052 transient effect Effects 0.000 claims description 10
- 239000011859 microparticle Substances 0.000 claims description 9
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 claims description 9
- HMJIYCCIJYRONP-UHFFFAOYSA-N (+-)-Isradipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC2=NON=C12 HMJIYCCIJYRONP-UHFFFAOYSA-N 0.000 claims description 8
- 229960001597 nifedipine Drugs 0.000 claims description 8
- PVHUJELLJLJGLN-INIZCTEOSA-N (S)-nitrendipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC([N+]([O-])=O)=C1 PVHUJELLJLJGLN-INIZCTEOSA-N 0.000 claims description 7
- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 claims description 7
- KJEBULYHNRNJTE-DHZHZOJOSA-N Cinalong Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC\C=C\C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 KJEBULYHNRNJTE-DHZHZOJOSA-N 0.000 claims description 7
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 claims description 7
- 229960000528 amlodipine Drugs 0.000 claims description 7
- 229960003020 cilnidipine Drugs 0.000 claims description 7
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 claims description 7
- 229960004166 diltiazem Drugs 0.000 claims description 7
- 229960003580 felodipine Drugs 0.000 claims description 7
- 229960000457 gallopamil Drugs 0.000 claims description 7
- 229960004427 isradipine Drugs 0.000 claims description 7
- VKQFCGNPDRICFG-UHFFFAOYSA-N methyl 2-methylpropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)C)C1C1=CC=CC=C1[N+]([O-])=O VKQFCGNPDRICFG-UHFFFAOYSA-N 0.000 claims description 7
- 229960000227 nisoldipine Drugs 0.000 claims description 7
- 229960005425 nitrendipine Drugs 0.000 claims description 7
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 claims description 6
- NSVFSAJIGAJDMR-UHFFFAOYSA-N 2-[benzyl(phenyl)amino]ethyl 5-(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate Chemical compound CC=1NC(C)=C(C(=O)OCCN(CC=2C=CC=CC=2)C=2C=CC=CC=2)C(C=2C=C(C=CC=2)[N+]([O-])=O)C=1P1(=O)OCC(C)(C)CO1 NSVFSAJIGAJDMR-UHFFFAOYSA-N 0.000 claims description 6
- XTFPDGZNWTZCMF-DHZHZOJOSA-N 3-o-methyl 5-o-[(e)-3-phenylprop-2-enyl] 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC\C=C\C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 XTFPDGZNWTZCMF-DHZHZOJOSA-N 0.000 claims description 6
- NCUCGYYHUFIYNU-UHFFFAOYSA-N Aranidipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)=O)C1C1=CC=CC=C1[N+]([O-])=O NCUCGYYHUFIYNU-UHFFFAOYSA-N 0.000 claims description 6
- XQLWNAFCTODIRK-UHFFFAOYSA-N Gallopamil Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC(OC)=C(OC)C(OC)=C1 XQLWNAFCTODIRK-UHFFFAOYSA-N 0.000 claims description 6
- WTOVRSWDBLIFHU-UHFFFAOYSA-N Lemildipine Chemical compound COC(=O)C1=C(C)NC(COC(N)=O)=C(C(=O)OC(C)C)C1C1=CC=CC(Cl)=C1Cl WTOVRSWDBLIFHU-UHFFFAOYSA-N 0.000 claims description 6
- FAIIFDPAEUKBEP-UHFFFAOYSA-N Nilvadipine Chemical compound COC(=O)C1=C(C#N)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC([N+]([O-])=O)=C1 FAIIFDPAEUKBEP-UHFFFAOYSA-N 0.000 claims description 6
- 229950007556 aranidipine Drugs 0.000 claims description 6
- QZVNQOLPLYWLHQ-ZEQKJWHPSA-N benidipine Chemical compound C1([C@H]2C(=C(C)NC(C)=C2C(=O)OC)C(=O)O[C@H]2CN(CC=3C=CC=CC=3)CCC2)=CC=CC([N+]([O-])=O)=C1 QZVNQOLPLYWLHQ-ZEQKJWHPSA-N 0.000 claims description 6
- 229960004916 benidipine Drugs 0.000 claims description 6
- UIEATEWHFDRYRU-UHFFFAOYSA-N bepridil Chemical compound C1CCCN1C(COCC(C)C)CN(C=1C=CC=CC=1)CC1=CC=CC=C1 UIEATEWHFDRYRU-UHFFFAOYSA-N 0.000 claims description 6
- 229960003665 bepridil Drugs 0.000 claims description 6
- 229920002988 biodegradable polymer Polymers 0.000 claims description 6
- 239000004621 biodegradable polymer Substances 0.000 claims description 6
- 229950003102 efonidipine Drugs 0.000 claims description 6
- 229960004340 lacidipine Drugs 0.000 claims description 6
- GKQPCPXONLDCMU-CCEZHUSRSA-N lacidipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1C1=CC=CC=C1\C=C\C(=O)OC(C)(C)C GKQPCPXONLDCMU-CCEZHUSRSA-N 0.000 claims description 6
- 229950001530 lemildipine Drugs 0.000 claims description 6
- ZDXUKAKRHYTAKV-UHFFFAOYSA-N lercanidipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)(C)CN(C)CCC(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZDXUKAKRHYTAKV-UHFFFAOYSA-N 0.000 claims description 6
- 229960004294 lercanidipine Drugs 0.000 claims description 6
- ANEBWFXPVPTEET-UHFFFAOYSA-N manidipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ANEBWFXPVPTEET-UHFFFAOYSA-N 0.000 claims description 6
- 229960003963 manidipine Drugs 0.000 claims description 6
- 229960005366 nilvadipine Drugs 0.000 claims description 6
- 229950004891 pranidipine Drugs 0.000 claims description 6
- 229960001722 verapamil Drugs 0.000 claims description 6
- ZKFQEACEUNWPMT-UHFFFAOYSA-N Azelnidipine Chemical compound CC(C)OC(=O)C1=C(C)NC(N)=C(C(=O)OC2CN(C2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZKFQEACEUNWPMT-UHFFFAOYSA-N 0.000 claims description 5
- 229950004646 azelnidipine Drugs 0.000 claims description 5
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 claims description 4
- 230000009969 flowable effect Effects 0.000 claims description 4
- 229940076372 protein antagonist Drugs 0.000 claims description 4
- 230000001839 systemic circulation Effects 0.000 claims description 4
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims description 2
- 229920000954 Polyglycolide Polymers 0.000 claims description 2
- 239000011159 matrix material Substances 0.000 claims description 2
- 229940122282 L-type calcium channel antagonist Drugs 0.000 claims 1
- 229960002992 barnidipine Drugs 0.000 claims 1
- VXMOONUMYLCFJD-DHLKQENFSA-N barnidipine Chemical compound C1([C@@H]2C(=C(C)NC(C)=C2C(=O)OC)C(=O)O[C@@H]2CN(CC=3C=CC=CC=3)CC2)=CC=CC([N+]([O-])=O)=C1 VXMOONUMYLCFJD-DHLKQENFSA-N 0.000 claims 1
- 229920000747 poly(lactic acid) Polymers 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 23
- 239000003795 chemical substances by application Substances 0.000 description 109
- 101710090554 Transient receptor potential protein Proteins 0.000 description 95
- 108090000765 processed proteins & peptides Proteins 0.000 description 89
- 102000003922 Calcium Channels Human genes 0.000 description 86
- 108090000312 Calcium Channels Proteins 0.000 description 85
- 239000000499 gel Substances 0.000 description 83
- 108091006146 Channels Proteins 0.000 description 55
- 239000003112 inhibitor Substances 0.000 description 50
- 229940079593 drug Drugs 0.000 description 46
- 238000012384 transportation and delivery Methods 0.000 description 45
- 206010002329 Aneurysm Diseases 0.000 description 43
- 229960003597 clevidipine Drugs 0.000 description 39
- KPBZROQVTHLCDU-GOSISDBHSA-N clevidipine Chemical compound CCCC(=O)OCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@H]1C1=CC=CC(Cl)=C1Cl KPBZROQVTHLCDU-GOSISDBHSA-N 0.000 description 39
- 239000011575 calcium Substances 0.000 description 37
- 210000004556 brain Anatomy 0.000 description 36
- 239000000126 substance Substances 0.000 description 36
- 150000003839 salts Chemical class 0.000 description 35
- 208000032843 Hemorrhage Diseases 0.000 description 32
- 108050001739 Endothelin receptor Proteins 0.000 description 31
- 102000010180 Endothelin receptor Human genes 0.000 description 31
- 210000001367 artery Anatomy 0.000 description 31
- 238000003556 assay Methods 0.000 description 31
- 208000024891 symptom Diseases 0.000 description 29
- 239000005557 antagonist Substances 0.000 description 28
- 230000027455 binding Effects 0.000 description 27
- 210000004369 blood Anatomy 0.000 description 27
- 239000008280 blood Substances 0.000 description 27
- 229910052791 calcium Inorganic materials 0.000 description 27
- 229940125400 channel inhibitor Drugs 0.000 description 27
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 26
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 26
- 238000009826 distribution Methods 0.000 description 26
- 239000007943 implant Substances 0.000 description 25
- 108090000623 proteins and genes Proteins 0.000 description 23
- 210000004204 blood vessel Anatomy 0.000 description 22
- 210000004027 cell Anatomy 0.000 description 22
- 239000000463 material Substances 0.000 description 21
- 201000008450 Intracranial aneurysm Diseases 0.000 description 20
- 208000034158 bleeding Diseases 0.000 description 20
- 229920000642 polymer Polymers 0.000 description 20
- 230000000740 bleeding effect Effects 0.000 description 19
- 238000009472 formulation Methods 0.000 description 19
- 206010047139 Vasoconstriction Diseases 0.000 description 18
- 230000036772 blood pressure Effects 0.000 description 18
- 235000018102 proteins Nutrition 0.000 description 18
- 102000004169 proteins and genes Human genes 0.000 description 18
- 230000025033 vasoconstriction Effects 0.000 description 18
- MOTJMGVDPWRKOC-QPVYNBJUSA-N atrasentan Chemical compound C1([C@H]2[C@@H]([C@H](CN2CC(=O)N(CCCC)CCCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C=C1 MOTJMGVDPWRKOC-QPVYNBJUSA-N 0.000 description 16
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 16
- 230000007423 decrease Effects 0.000 description 16
- 230000009885 systemic effect Effects 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 101800004490 Endothelin-1 Proteins 0.000 description 15
- 230000000747 cardiac effect Effects 0.000 description 15
- 238000002591 computed tomography Methods 0.000 description 15
- 230000006870 function Effects 0.000 description 15
- 238000011534 incubation Methods 0.000 description 15
- 102000004196 processed proteins & peptides Human genes 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- 102000002045 Endothelin Human genes 0.000 description 14
- 108050009340 Endothelin Proteins 0.000 description 14
- 206010020772 Hypertension Diseases 0.000 description 14
- 241001465754 Metazoa Species 0.000 description 14
- 238000002583 angiography Methods 0.000 description 13
- 230000003111 delayed effect Effects 0.000 description 13
- 201000010099 disease Diseases 0.000 description 13
- 208000035475 disorder Diseases 0.000 description 13
- 210000002216 heart Anatomy 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 230000024883 vasodilation Effects 0.000 description 13
- 108091023044 voltage-gated calcium channel activity Proteins 0.000 description 13
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 12
- 239000013543 active substance Substances 0.000 description 12
- 210000004004 carotid artery internal Anatomy 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 239000003153 chemical reaction reagent Substances 0.000 description 12
- 208000028867 ischemia Diseases 0.000 description 12
- 239000002245 particle Substances 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 12
- 102000038650 voltage-gated calcium channel activity Human genes 0.000 description 12
- 208000001953 Hypotension Diseases 0.000 description 11
- 230000004913 activation Effects 0.000 description 11
- 230000008901 benefit Effects 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 230000036543 hypotension Effects 0.000 description 11
- 230000001965 increasing effect Effects 0.000 description 11
- 230000003834 intracellular effect Effects 0.000 description 11
- KBPZBOSJIZEELA-UHFFFAOYSA-N 1-[2-[4-methoxy-3-[3-(4-methoxyphenyl)propoxy]phenyl]ethyl]imidazole;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1CCCOC1=CC(CCN2C=NC=C2)=CC=C1OC KBPZBOSJIZEELA-UHFFFAOYSA-N 0.000 description 10
- PYWYBTRACMRUQV-UHFFFAOYSA-N 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)-2-phenyl-n,n-bis[2-(2,3,4-trimethoxyphenyl)ethyl]acetamide Chemical compound COC1=C(OC)C(OC)=CC=C1CCN(C(=O)C(C=1C2=CC(OC)=C(OC)C=C2CCN=1)C=1C=CC=CC=1)CCC1=CC=C(OC)C(OC)=C1OC PYWYBTRACMRUQV-UHFFFAOYSA-N 0.000 description 10
- 102100033902 Endothelin-1 Human genes 0.000 description 10
- 208000006011 Stroke Diseases 0.000 description 10
- 239000000872 buffer Substances 0.000 description 10
- 230000006378 damage Effects 0.000 description 10
- 239000003937 drug carrier Substances 0.000 description 10
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 10
- 230000007246 mechanism Effects 0.000 description 10
- 239000012528 membrane Substances 0.000 description 10
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 230000004044 response Effects 0.000 description 10
- 206010019196 Head injury Diseases 0.000 description 9
- 102000004310 Ion Channels Human genes 0.000 description 9
- 108090000862 Ion Channels Proteins 0.000 description 9
- 108090000420 L-Type Calcium Channels Proteins 0.000 description 9
- 102000004016 L-Type Calcium Channels Human genes 0.000 description 9
- 102000004059 R-Type Calcium Channels Human genes 0.000 description 9
- 108090000583 R-Type Calcium Channels Proteins 0.000 description 9
- 230000009471 action Effects 0.000 description 9
- 229950007733 clazosentan Drugs 0.000 description 9
- 238000003745 diagnosis Methods 0.000 description 9
- 230000003993 interaction Effects 0.000 description 9
- 210000003657 middle cerebral artery Anatomy 0.000 description 9
- 210000002464 muscle smooth vascular Anatomy 0.000 description 9
- LFWCJABOXHSRGC-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[2-(2h-tetrazol-5-yl)pyridin-4-yl]pyrimidin-4-yl]-5-methylpyridine-2-sulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(N=CC=2)C2=NNN=N2)OCCO)=C1NS(=O)(=O)C1=CC=C(C)C=N1 LFWCJABOXHSRGC-UHFFFAOYSA-N 0.000 description 9
- 229920001223 polyethylene glycol Polymers 0.000 description 9
- 238000000159 protein binding assay Methods 0.000 description 9
- 239000003071 vasodilator agent Substances 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000012190 activator Substances 0.000 description 8
- 229950010993 atrasentan Drugs 0.000 description 8
- 230000000903 blocking effect Effects 0.000 description 8
- 208000029028 brain injury Diseases 0.000 description 8
- 230000003247 decreasing effect Effects 0.000 description 8
- 229940088679 drug related substance Drugs 0.000 description 8
- 230000007574 infarction Effects 0.000 description 8
- 208000014674 injury Diseases 0.000 description 8
- 150000002500 ions Chemical class 0.000 description 8
- 230000028161 membrane depolarization Effects 0.000 description 8
- 210000002569 neuron Anatomy 0.000 description 8
- 230000036581 peripheral resistance Effects 0.000 description 8
- 210000003388 posterior cerebral artery Anatomy 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 230000001105 regulatory effect Effects 0.000 description 8
- 210000002460 smooth muscle Anatomy 0.000 description 8
- 229940124549 vasodilator Drugs 0.000 description 8
- 206010019233 Headaches Diseases 0.000 description 7
- 206010061216 Infarction Diseases 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 210000002551 anterior cerebral artery Anatomy 0.000 description 7
- 210000001841 basilar artery Anatomy 0.000 description 7
- 230000006931 brain damage Effects 0.000 description 7
- 231100000874 brain damage Toxicity 0.000 description 7
- 239000000969 carrier Substances 0.000 description 7
- 210000000170 cell membrane Anatomy 0.000 description 7
- 235000014113 dietary fatty acids Nutrition 0.000 description 7
- 239000000194 fatty acid Substances 0.000 description 7
- 229930195729 fatty acid Natural products 0.000 description 7
- 239000000017 hydrogel Substances 0.000 description 7
- 230000000670 limiting effect Effects 0.000 description 7
- 239000011148 porous material Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- 206010007686 Carotid artery aneurysm Diseases 0.000 description 6
- 108091005462 Cation channels Proteins 0.000 description 6
- 108020004202 Guanylate Kinase Proteins 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 230000004872 arterial blood pressure Effects 0.000 description 6
- 229940049706 benzodiazepine Drugs 0.000 description 6
- 150000001557 benzodiazepines Chemical class 0.000 description 6
- 230000003727 cerebral blood flow Effects 0.000 description 6
- 206010008118 cerebral infarction Diseases 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000011248 coating agent Substances 0.000 description 6
- 230000008602 contraction Effects 0.000 description 6
- 239000002872 contrast media Substances 0.000 description 6
- 150000004665 fatty acids Chemical class 0.000 description 6
- 239000012530 fluid Substances 0.000 description 6
- 229940075507 glyceryl monostearate Drugs 0.000 description 6
- 102000006638 guanylate kinase Human genes 0.000 description 6
- 210000003128 head Anatomy 0.000 description 6
- 231100000869 headache Toxicity 0.000 description 6
- 208000003906 hydrocephalus Diseases 0.000 description 6
- 238000002513 implantation Methods 0.000 description 6
- 230000004941 influx Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 230000007774 longterm Effects 0.000 description 6
- 238000009593 lumbar puncture Methods 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 6
- 229930014626 natural product Natural products 0.000 description 6
- 230000001537 neural effect Effects 0.000 description 6
- 150000002894 organic compounds Chemical class 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000004393 prognosis Methods 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 150000003384 small molecules Chemical class 0.000 description 6
- 238000001308 synthesis method Methods 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 230000000472 traumatic effect Effects 0.000 description 6
- 230000002792 vascular Effects 0.000 description 6
- 210000002385 vertebral artery Anatomy 0.000 description 6
- 102400000687 Big endothelin-1 Human genes 0.000 description 5
- 101800001398 Big endothelin-1 Proteins 0.000 description 5
- 201000006474 Brain Ischemia Diseases 0.000 description 5
- 206010008120 Cerebral ischaemia Diseases 0.000 description 5
- 206010010071 Coma Diseases 0.000 description 5
- 206010010904 Convulsion Diseases 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 102000004129 N-Type Calcium Channels Human genes 0.000 description 5
- 108090000699 N-Type Calcium Channels Proteins 0.000 description 5
- 108050001421 Transient receptor potential channel, canonical 6 Proteins 0.000 description 5
- 102000014384 Type C Phospholipases Human genes 0.000 description 5
- 108010079194 Type C Phospholipases Proteins 0.000 description 5
- 208000027418 Wounds and injury Diseases 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 239000008186 active pharmaceutical agent Substances 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 230000003872 anastomosis Effects 0.000 description 5
- 238000002399 angioplasty Methods 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- HZZGDPLAJHVHSP-GKHTVLBPSA-N big endothelin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]2CSSC[C@@H](C(N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CSSC1)C1=CN=CN1 HZZGDPLAJHVHSP-GKHTVLBPSA-N 0.000 description 5
- 230000017531 blood circulation Effects 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 230000004087 circulation Effects 0.000 description 5
- 238000000576 coating method Methods 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 239000000839 emulsion Substances 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 238000002595 magnetic resonance imaging Methods 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 239000004005 microsphere Substances 0.000 description 5
- 210000003205 muscle Anatomy 0.000 description 5
- 229920001184 polypeptide Polymers 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 210000001908 sarcoplasmic reticulum Anatomy 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- 239000000375 suspending agent Substances 0.000 description 5
- UUAVCCWBNUITBB-UPRLRBBYSA-N (1s,2r,3s)-1-(1,3-benzodioxol-5-yl)-3-[2-(carboxymethoxy)-4-methoxyphenyl]-5-propoxy-2,3-dihydro-1h-indene-2-carboxylic acid Chemical compound C1([C@H]2[C@@H]([C@H](C3=CC=C(C=C32)OCCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C=C1OCC(O)=O UUAVCCWBNUITBB-UPRLRBBYSA-N 0.000 description 4
- JVILFANCFWZBFU-ZGIBFIJWSA-N (2r)-2-[[(2r)-2-[[(2s)-2-(azepane-1-carbonylamino)-4-methylpentanoyl]amino]-3-(1-methylindol-3-yl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@H](CC=1C2=CC=CC=C2N(C)C=1)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(O)=O)C(=O)N1CCCCCC1 JVILFANCFWZBFU-ZGIBFIJWSA-N 0.000 description 4
- LIOKMIQQPDDTNO-UPRLRBBYSA-N (2r)-2-[[(2r)-2-[[(2s)-2-(azepane-1-carbonylamino)-4-methylpentanoyl]amino]-3-(1-methylindol-3-yl)propanoyl]amino]-3-pyridin-2-ylpropanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@H](CC=1C2=CC=CC=C2N(C)C=1)C(=O)N[C@H](CC=1N=CC=CC=1)C(O)=O)C(=O)N1CCCCCC1 LIOKMIQQPDDTNO-UPRLRBBYSA-N 0.000 description 4
- QVTBFVFPWXEIOX-VYAQOJDXSA-N (2r)-2-[[(2s)-2-[3-[[(2r)-2-[[(2r)-2-[[(2s)-2-(azepane-1-carbonylamino)-4-methylpentanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]propanoyl]amino]propanoylamino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-phenylpropanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](C)C(=O)NCCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CC=1C=CC=CC=1)C(O)=O)C(=O)N1CCCCCC1 QVTBFVFPWXEIOX-VYAQOJDXSA-N 0.000 description 4
- LQEHCKYYIXQEBM-FUKIBTTHSA-N (2r,3r,4s)-4-(1,3-benzodioxol-5-yl)-1-[2-(2,6-diethylanilino)-2-oxoethyl]-2-(4-propoxyphenyl)pyrrolidine-3-carboxylic acid Chemical compound C1=CC(OCCC)=CC=C1[C@@H]1N(CC(=O)NC=2C(=CC=CC=2CC)CC)C[C@H](C=2C=C3OCOC3=CC=2)[C@H]1C(O)=O LQEHCKYYIXQEBM-FUKIBTTHSA-N 0.000 description 4
- CMTKCIMTAINHTK-OMETZTOSSA-N (2r,3r,4s)-4-(1,3-benzodioxol-5-yl)-1-[2-[bis(2-methylphenyl)methylamino]-2-oxoethyl]-2-[4-(2-propan-2-yloxyethoxy)phenyl]pyrrolidine-3-carboxylic acid Chemical compound C1=CC(OCCOC(C)C)=CC=C1[C@@H]1N(CC(=O)NC(C=2C(=CC=CC=2)C)C=2C(=CC=CC=2)C)C[C@H](C=2C=C3OCOC3=CC=2)[C@H]1C(O)=O CMTKCIMTAINHTK-OMETZTOSSA-N 0.000 description 4
- UZDORQWMYRRLQV-JHOUSYSJSA-N (2s)-2-[[(2r)-2-[(3,5-dimethylbenzoyl)-methylamino]-3-(4-phenylphenyl)propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C([C@@H](N(C)C(=O)C=1C=C(C)C=C(C)C=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=CC=C1 UZDORQWMYRRLQV-JHOUSYSJSA-N 0.000 description 4
- HYNSSBPBTFFZKW-OUPFVLIJSA-N (2s)-2-amino-3-[(2s)-2-[[(2r)-1-[[(2s)-1-[[(2r)-1-(1h-indol-3-yl)-3-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]-2,5-dihydropyrrol-1-yl]-3-oxopropane-1-sulfonic acid Chemical compound N([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C=O)C(C)C)C(=O)[C@@H]1C=CCN1C(=O)[C@H](N)CS(O)(=O)=O HYNSSBPBTFFZKW-OUPFVLIJSA-N 0.000 description 4
- OETKRDJJNWJFOP-FAYOUAAYSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[[(4S,7S,10S,13S,16R)-16-amino-7-benzyl-10-[(4-hydroxyphenyl)methyl]-6,9,12,15-tetraoxo-13-propan-2-yl-1,2-dithia-5,8,11,14-tetrazacycloheptadecane-4-carbonyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-4-[[(2S,3S)-1-[[(2S,3S)-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-oxobutanoic acid Chemical compound CC[C@H](C)[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H]1CSSC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](Cc2ccccc2)C(=O)N1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(O)=O OETKRDJJNWJFOP-FAYOUAAYSA-N 0.000 description 4
- MBHURWYWZFYDQD-HDUXTRFBSA-N (4r)-4-[[(2r)-2-[[(2s)-2-[[(2r,3s)-2-[[(2s)-2-aminopropanoyl]amino]-3-methylpentanoyl]amino]-4-methylpent-4-enoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]-5-oxopentanoic acid Chemical compound C1=CC=C2C(C[C@@H](NC(=O)[C@H](CC(C)=C)NC(=O)[C@H](NC(=O)[C@H](C)N)[C@@H](C)CC)C(=O)N[C@H](CCC(O)=O)C=O)=CNC2=C1 MBHURWYWZFYDQD-HDUXTRFBSA-N 0.000 description 4
- QGTFISXASKMOQM-MPPIKMIVSA-N (4r)-4-amino-5-[(2s)-2-[[(2r)-1-[[(2s)-1-[[(2r)-1-(1h-indol-3-yl)-3-oxopropan-2-yl]amino]-4-methyl-1-oxopent-4-en-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-5-oxopentanoic acid Chemical compound N([C@H](C(C)C)C(=O)N[C@@H](CC(C)=C)C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C=O)C(=O)[C@@H]1CCCN1C(=O)[C@H](N)CCC(O)=O QGTFISXASKMOQM-MPPIKMIVSA-N 0.000 description 4
- IUHMIOAKWHUFKU-YINIXLNUSA-N (5s,6r,7r)-5-(1,3-benzodioxol-5-yl)-2-butyl-7-[2-[(2s)-2-carboxypropyl]-4-methoxyphenyl]-6,7-dihydro-5h-cyclopenta[b]pyridine-6-carboxylic acid Chemical compound C1([C@H]2[C@@H]([C@H](C3=CC=C(N=C32)CCCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C=C1C[C@H](C)C(O)=O IUHMIOAKWHUFKU-YINIXLNUSA-N 0.000 description 4
- QVEGXHOZQYEMHS-BUVRLJJBSA-N 2-[[2-[2-butyl-4-[(e)-2-carboxy-3-(5-methoxy-2,3-dihydro-1-benzofuran-6-yl)prop-1-enyl]pyrazol-3-yl]-5-chlorophenoxy]methyl]benzoic acid Chemical compound CCCCN1N=CC(\C=C(/CC=2C(=CC=3CCOC=3C=2)OC)C(O)=O)=C1C1=CC=C(Cl)C=C1OCC1=CC=CC=C1C(O)=O QVEGXHOZQYEMHS-BUVRLJJBSA-N 0.000 description 4
- LIOKMIQQPDDTNO-UHFFFAOYSA-N 2-[[2-[[2-[[1-azepanyl(oxo)methyl]amino]-4-methyl-1-oxopentyl]amino]-3-(1-methyl-3-indolyl)-1-oxopropyl]amino]-3-(2-pyridinyl)propanoic acid Chemical compound C=1N(C)C2=CC=CC=C2C=1CC(C(=O)NC(CC=1N=CC=CC=1)C(O)=O)NC(=O)C(CC(C)C)NC(=O)N1CCCCCC1 LIOKMIQQPDDTNO-UHFFFAOYSA-N 0.000 description 4
- QAMIWBVQNOICHO-XZOQPEGZSA-N 3-[[(2r)-2-[[(2s)-2-(azepane-1-carbonylamino)-4-methylpentanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]propanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCCC(O)=O)C(=O)N1CCCCCC1 QAMIWBVQNOICHO-XZOQPEGZSA-N 0.000 description 4
- MJRGSRRZKSJHOE-UHFFFAOYSA-N 5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamide Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(=O)(=O)NC=1ON=C(C)C=1C MJRGSRRZKSJHOE-UHFFFAOYSA-N 0.000 description 4
- PZNZOWSLQRURNA-HNRBIFIRSA-N 5-o-[(4s)-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carbonyl] 3-o-methyl (4r)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound C1([C@@H]2C(=C(C)NC(C)=C2C(=O)OC)C(=O)OC(=O)C=2[C@@H](C(=C(C)NC=2C)C(=O)OC)C=2C=C(C=CC=2)[N+]([O-])=O)=CC=CC([N+]([O-])=O)=C1 PZNZOWSLQRURNA-HNRBIFIRSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 4
- 201000001320 Atherosclerosis Diseases 0.000 description 4
- VYCMAAOURFJIHD-PJNXIOHISA-N BQ 123 Chemical compound N1C(=O)[C@H](CC(C)C)NC(=O)[C@@H](C(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@@H](CC(O)=O)NC(=O)[C@H]1CC1=CNC2=CC=CC=C12 VYCMAAOURFJIHD-PJNXIOHISA-N 0.000 description 4
- 108010080719 BQ 485 Proteins 0.000 description 4
- ZBJNAHVLKNFOPP-OJDZSJEKSA-N BQ 485 Chemical compound N([C@@H](CC(C)C)C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C(=O)N1CCCCCC1 ZBJNAHVLKNFOPP-OJDZSJEKSA-N 0.000 description 4
- KXUDUVUGZWJNHV-QEXRHJMMSA-N BQ 518 Chemical compound C1([C@@H]2C(=O)N[C@H](C(N[C@H](CC=3C4=CC=CC=C4NC=3)C(=O)N[C@H](CC(O)=O)C(=O)N3CCC[C@H]3C(=O)N2)=O)CC(C)C)=CC=CS1 KXUDUVUGZWJNHV-QEXRHJMMSA-N 0.000 description 4
- 108010030109 BQ 788 Proteins 0.000 description 4
- KJNNBRVUQZDOET-AREMUKBSSA-N CCCC1=NC(C)=CC=C1O[C@H](C=1C=C2OCOC2=CC=1)C(=O)NS(=O)(=O)C1=CC=C(C(C)C)C=C1 Chemical compound CCCC1=NC(C)=CC=C1O[C@H](C=1C=C2OCOC2=CC=1)C(=O)NS(=O)(=O)C1=CC=C(C(C)C)C=C1 KJNNBRVUQZDOET-AREMUKBSSA-N 0.000 description 4
- 108010069674 CP 170687 Proteins 0.000 description 4
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 4
- 206010053942 Cerebral haematoma Diseases 0.000 description 4
- 108010034003 Cys(11)-Cys(15)-endothelin-1 (11-21) Proteins 0.000 description 4
- 102100040611 Endothelin receptor type B Human genes 0.000 description 4
- 108010072844 Endothelin-3 Proteins 0.000 description 4
- 102100029109 Endothelin-3 Human genes 0.000 description 4
- 108030001679 Endothelin-converting enzyme 1 Proteins 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- 101000637699 Homo sapiens Ryanodine receptor 1 Proteins 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 108010024468 IRL 2500 Proteins 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- 206010022840 Intraventricular haemorrhage Diseases 0.000 description 4
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- 108010009124 PD 142893 Proteins 0.000 description 4
- 108010007647 PD 145065 Proteins 0.000 description 4
- 108010058337 PD 151242 Proteins 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 108010053959 RES 701-1 Proteins 0.000 description 4
- 102100032122 Ryanodine receptor 1 Human genes 0.000 description 4
- 229930182558 Sterol Natural products 0.000 description 4
- 108010047918 TAK 044 Proteins 0.000 description 4
- 102000027549 TRPC Human genes 0.000 description 4
- 108060008648 TRPC Proteins 0.000 description 4
- 108010078577 TTA 386 Proteins 0.000 description 4
- 102000011213 Transient receptor potential channel, canonical 6 Human genes 0.000 description 4
- 206010047700 Vomiting Diseases 0.000 description 4
- PGAVKCOVUIYSFO-UHFFFAOYSA-N [[5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound OC1C(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-UHFFFAOYSA-N 0.000 description 4
- 229960001138 acetylsalicylic acid Drugs 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 210000000576 arachnoid Anatomy 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 4
- 230000036770 blood supply Effects 0.000 description 4
- GJPICJJJRGTNOD-UHFFFAOYSA-N bosentan Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 GJPICJJJRGTNOD-UHFFFAOYSA-N 0.000 description 4
- 229960003065 bosentan Drugs 0.000 description 4
- 229910001424 calcium ion Inorganic materials 0.000 description 4
- 150000001768 cations Chemical class 0.000 description 4
- ZGOVYTPSWMLYOF-QEADGSHQSA-N chembl1790180 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CC=3C=CC=CC=3)C(=O)N[C@H](C(=O)N[C@H](CCC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)[C@H](C)O)=O)NC(=O)[C@@H]([C@@H](C)O)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZGOVYTPSWMLYOF-QEADGSHQSA-N 0.000 description 4
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 4
- 210000000275 circle of willis Anatomy 0.000 description 4
- 108010031322 cyclo(Trp-Asp-Pro-Val-Leu) Proteins 0.000 description 4
- 108010017327 cyclo(glutamyl-alanyl-isoleucyl-leucyl-tryptophyl) Proteins 0.000 description 4
- 108010012014 cyclo(glutamyl-prolyl-valyl-leucyl-tryptophyl) Proteins 0.000 description 4
- 108010055679 cyclo(sulfoalanyl-prolyl-valyl-leucyl-tryptophyl) Proteins 0.000 description 4
- 108010005235 cyclo(tryptophyl-aspartyl-acetyl(3)c-valyl-leucyl) Proteins 0.000 description 4
- 108010035609 cyclo(tryptophyl-aspartyl-prolyl-thianylglycyl-leucyl) Proteins 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- UWHBIISPHYTOGL-PFSAEEMXSA-L disodium;2-[(2r,5s,8s,11s,14s,17r)-8-(carboxylatomethyl)-17-(1h-indol-3-ylmethyl)-14-(2-methylpropyl)-3,6,9,12,15,18-hexaoxo-5-[2-oxo-2-(4-phenylpiperazin-1-yl)ethyl]-11-thiophen-2-yl-1,4,7,10,13,16-hexazacyclooctadec-2-yl]acetate Chemical compound [Na+].[Na+].C([C@H]1C(=O)N[C@@H](CC([O-])=O)C(=O)N[C@@H](C(=O)N[C@H](C(N[C@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@H](CC([O-])=O)C(=O)N1)=O)CC(C)C)C=1SC=CC=1)C(=O)N(CC1)CCN1C1=CC=CC=C1 UWHBIISPHYTOGL-PFSAEEMXSA-L 0.000 description 4
- 239000002270 dispersing agent Substances 0.000 description 4
- XIIPOLLCNQAOCP-XQTCEJMISA-N dnc012318 Chemical compound C([C@@H]1C(=O)NCC(=O)N[C@@H](C(N[C@@H](C)C(=O)N2CCC[C@@H]2C(=O)N[C@H](CC(=O)NCC(=O)N[C@H](CC(N)=O)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)=O)[C@H](O)C)C1=CNC=N1 XIIPOLLCNQAOCP-XQTCEJMISA-N 0.000 description 4
- 210000002889 endothelial cell Anatomy 0.000 description 4
- GLCKXJLCYIJMRB-UPRLRBBYSA-N enrasentan Chemical compound C1([C@H]2[C@@H]([C@H](C3=CC=C(C=C32)OCCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C=C1OCCO GLCKXJLCYIJMRB-UPRLRBBYSA-N 0.000 description 4
- 230000004927 fusion Effects 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 230000000004 hemodynamic effect Effects 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 238000007917 intracranial administration Methods 0.000 description 4
- 238000007913 intrathecal administration Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- 210000001259 mesencephalon Anatomy 0.000 description 4
- 210000004165 myocardium Anatomy 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 210000001636 ophthalmic artery Anatomy 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 239000008177 pharmaceutical agent Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- VGEREEWJJVICBM-UHFFFAOYSA-N phloretin Chemical compound C1=CC(O)=CC=C1CCC(=O)C1=C(O)C=C(O)C=C1O VGEREEWJJVICBM-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 230000011514 reflex Effects 0.000 description 4
- 229960002578 sitaxentan Drugs 0.000 description 4
- PHWXUGHIIBDVKD-UHFFFAOYSA-N sitaxentan Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)CC=2C(=CC=3OCOC=3C=2)C)=C1Cl PHWXUGHIIBDVKD-UHFFFAOYSA-N 0.000 description 4
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 4
- NSUPRLHDCFNOKD-UHFFFAOYSA-N snx 482 Chemical compound N1C(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)CNC(=O)C(C)NC(=O)C(CCCCN)NC(=O)C(CC(O)=O)NC(=O)C(NC(=O)CN)C(C)C)CSSCC(C(N2CCCC2C(=O)NC(CCCNC(N)=N)C(=O)NC(CC(C)C)C(=O)NCC(=O)N2)=O)NC(=O)C(NC(=O)C(CC(O)=O)NC(=O)C(CC(O)=O)NC(=O)C(CC(N)=O)NC(=O)C(C(C)C)NC(=O)C(CO)NC3=O)CSSCC(C(=O)NC(C)C(=O)NC(CC=4C5=CC=CC=C5NC=4)C(=O)NC(CC(O)=O)C(=O)NC(CC(C)C)C(=O)NC(C(C)O)C(=O)NC(CC=4C=CC=CC=4)C(=O)NC(CO)C(=O)NC(CC(O)=O)C(O)=O)NC(=O)C(CC=4C=CC(O)=CC=4)NC(=O)C(CO)NC(=O)C(CC=4C=CC=CC=4)NC(=O)C(CC(C)C)NC(=O)C(CO)NC(=O)C(CC=4N=CNC=4)NC(=O)C2CSSCC3NC(=O)CNC(=O)CNC(=O)C(CC=2C=CC=CC=2)NC(=O)C(CCSC)NC(=O)C1CC1=CC=C(O)C=C1 NSUPRLHDCFNOKD-UHFFFAOYSA-N 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- QCVIFBRTTLMEOV-FUKQNADPSA-M sodium;(2r)-2-[[(2r)-2-[[(2s)-2-[[(2s,6r)-2,6-dimethylpiperidine-1-carbonyl]amino]-4,4-dimethylpentanoyl]amino]-3-(1-methoxycarbonylindol-3-yl)propanoyl]amino]hexanoate Chemical compound [Na+].N([C@@H](CC(C)(C)C)C(=O)N[C@H](CC=1C2=CC=CC=C2N(C(=O)OC)C=1)C(=O)N[C@H](CCCC)C([O-])=O)C(=O)N1[C@@H](C)CCC[C@H]1C QCVIFBRTTLMEOV-FUKQNADPSA-M 0.000 description 4
- MDTNUYUCUYPIHE-UHFFFAOYSA-N sodium;(4-chloro-3-methyl-1,2-oxazol-5-yl)-[2-[2-(6-methyl-1,3-benzodioxol-5-yl)acetyl]thiophen-3-yl]sulfonylazanide Chemical compound [Na+].CC1=NOC([N-]S(=O)(=O)C2=C(SC=C2)C(=O)CC=2C(=CC=3OCOC=3C=2)C)=C1Cl MDTNUYUCUYPIHE-UHFFFAOYSA-N 0.000 description 4
- 150000003432 sterols Chemical class 0.000 description 4
- 235000003702 sterols Nutrition 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 239000005526 vasoconstrictor agent Substances 0.000 description 4
- 230000008673 vomiting Effects 0.000 description 4
- QHSRPPJQBFQWSC-OJDZSJEKSA-N (2r)-2-[[(2r)-2-[[(2s)-2-(azepane-1-carbonylamino)-4-methylpentanoyl]amino]-3-(1-formylindol-3-yl)propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@H](CC=1C2=CC=CC=C2N(C=O)C=1)C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C(=O)N1CCCCCC1 QHSRPPJQBFQWSC-OJDZSJEKSA-N 0.000 description 3
- JVWVTPZZEHLARL-OFEZKSIWSA-N (2r,3r,4s)-4-(1,3-benzodioxol-5-yl)-2-(3-fluoro-4-methoxyphenyl)-1-[2-[pentylsulfonyl(propyl)amino]ethyl]pyrrolidine-3-carboxylic acid Chemical compound C1([C@H]2[C@@H]([C@H](CN2CCN(CCC)S(=O)(=O)CCCCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C(F)=C1 JVWVTPZZEHLARL-OFEZKSIWSA-N 0.000 description 3
- CDBNTQYPMBJKQZ-UHFFFAOYSA-N 3-[4-[3-[(3-methoxy-5-methylpyrazin-2-yl)sulfamoyl]pyridin-2-yl]phenyl]-2,2-dimethylpropanoic acid Chemical compound COC1=NC(C)=CN=C1NS(=O)(=O)C1=CC=CN=C1C1=CC=C(CC(C)(C)C(O)=O)C=C1 CDBNTQYPMBJKQZ-UHFFFAOYSA-N 0.000 description 3
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 108010088751 Albumins Proteins 0.000 description 3
- 102000009027 Albumins Human genes 0.000 description 3
- 108010073982 BQ 610 Proteins 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 208000022540 Consciousness disease Diseases 0.000 description 3
- 108010016626 Dipeptides Proteins 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 102000048186 Endothelin-converting enzyme 1 Human genes 0.000 description 3
- 102100029112 Endothelin-converting enzyme 1 Human genes 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 102000016349 Myosin Light Chains Human genes 0.000 description 3
- 108010067385 Myosin Light Chains Proteins 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 102000050761 P/Q-type calcium channel Human genes 0.000 description 3
- 108700012358 P/Q-type calcium channel Proteins 0.000 description 3
- 208000007542 Paresis Diseases 0.000 description 3
- 108010043958 Peptoids Proteins 0.000 description 3
- ZPHBZEQOLSRPAK-UHFFFAOYSA-N Phosphoramidon Natural products C=1NC2=CC=CC=C2C=1CC(C(O)=O)NC(=O)C(CC(C)C)NP(O)(=O)OC1OC(C)C(O)C(O)C1O ZPHBZEQOLSRPAK-UHFFFAOYSA-N 0.000 description 3
- 229920002732 Polyanhydride Polymers 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 102000004257 Potassium Channel Human genes 0.000 description 3
- 208000018238 Primary Headache disease Diseases 0.000 description 3
- 206010037423 Pulmonary oedema Diseases 0.000 description 3
- 208000004717 Ruptured Aneurysm Diseases 0.000 description 3
- FWLPKVQUECFKSW-UHFFFAOYSA-N SKF-96365 hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1CCCOC(C=1C=CC(OC)=CC=1)CN1C=NC=C1 FWLPKVQUECFKSW-UHFFFAOYSA-N 0.000 description 3
- 108010067223 TRPC3 cation channel Proteins 0.000 description 3
- 208000007536 Thrombosis Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- PGAVKCOVUIYSFO-XVFCMESISA-N UTP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-XVFCMESISA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 230000004075 alteration Effects 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 230000003042 antagnostic effect Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000000423 cell based assay Methods 0.000 description 3
- 230000003788 cerebral perfusion Effects 0.000 description 3
- 210000004720 cerebrum Anatomy 0.000 description 3
- 238000007385 chemical modification Methods 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 231100000517 death Toxicity 0.000 description 3
- 230000006735 deficit Effects 0.000 description 3
- 238000000151 deposition Methods 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000003599 detergent Substances 0.000 description 3
- 238000002059 diagnostic imaging Methods 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 230000010339 dilation Effects 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 238000002337 electrophoretic mobility shift assay Methods 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 210000001652 frontal lobe Anatomy 0.000 description 3
- 230000002538 fungal effect Effects 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 3
- 206010019465 hemiparesis Diseases 0.000 description 3
- 238000013537 high throughput screening Methods 0.000 description 3
- 238000012188 high-throughput screening assay Methods 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 230000002779 inactivation Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000000297 inotrophic effect Effects 0.000 description 3
- 210000002425 internal capsule Anatomy 0.000 description 3
- 238000001361 intraarterial administration Methods 0.000 description 3
- 230000000302 ischemic effect Effects 0.000 description 3
- 238000012917 library technology Methods 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 238000007726 management method Methods 0.000 description 3
- 230000004001 molecular interaction Effects 0.000 description 3
- 230000004118 muscle contraction Effects 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 230000000926 neurological effect Effects 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000000346 nonvolatile oil Substances 0.000 description 3
- 238000005457 optimization Methods 0.000 description 3
- 230000000149 penetrating effect Effects 0.000 description 3
- 239000000816 peptidomimetic Substances 0.000 description 3
- 238000002823 phage display Methods 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- BWSDNRQVTFZQQD-AYVHNPTNSA-N phosphoramidon Chemical compound O([P@@](O)(=O)N[C@H](CC(C)C)C(=O)N[C@H](CC=1[C]2C=CC=CC2=NC=1)C(O)=O)[C@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@@H]1O BWSDNRQVTFZQQD-AYVHNPTNSA-N 0.000 description 3
- 108010072906 phosphoramidon Proteins 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 108020001213 potassium channel Proteins 0.000 description 3
- 230000006916 protein interaction Effects 0.000 description 3
- 150000003212 purines Chemical class 0.000 description 3
- 150000003230 pyrimidines Chemical class 0.000 description 3
- 229940044551 receptor antagonist Drugs 0.000 description 3
- 239000002464 receptor antagonist Substances 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 210000002027 skeletal muscle Anatomy 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- RSGMPVJSBAIOBP-IJVOEZGUSA-M sodium;(z)-2-(2,1,3-benzothiadiazol-5-yl)-4-(3-fluoro-4-methoxyphenyl)-4-oxo-3-[(3,4,5-trimethoxyphenyl)methyl]but-2-enoate Chemical compound [Na+].C1=C(F)C(OC)=CC=C1C(=O)C(\CC=1C=C(OC)C(OC)=C(OC)C=1)=C(/C([O-])=O)C1=CC2=NSN=C2C=C1 RSGMPVJSBAIOBP-IJVOEZGUSA-M 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 210000002820 sympathetic nervous system Anatomy 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 150000003505 terpenes Chemical class 0.000 description 3
- 238000010399 three-hybrid screening Methods 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 230000008733 trauma Effects 0.000 description 3
- 238000010396 two-hybrid screening Methods 0.000 description 3
- 229950010342 uridine triphosphate Drugs 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- 210000004885 white matter Anatomy 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- WTIMYTIFDDIBIP-SNUHDYGFSA-N (2r)-2-[[(2r)-3-(2-cyano-1h-indol-3-yl)-2-[[(2s)-2-[[(2r,6s)-2,6-dimethylpiperidine-1-carbonyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]hexanoic acid Chemical compound N([C@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1C#N)C(=O)N[C@H](CCCC)C(O)=O)C(C)C)C(=O)N1[C@@H](C)CCC[C@H]1C WTIMYTIFDDIBIP-SNUHDYGFSA-N 0.000 description 2
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 102000000584 Calmodulin Human genes 0.000 description 2
- 108010041952 Calmodulin Proteins 0.000 description 2
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 2
- 102000034573 Channels Human genes 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 241000272095 Dendroaspis angusticeps Species 0.000 description 2
- 206010012373 Depressed level of consciousness Diseases 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 2
- 102000003965 Endothelin-2 Human genes 0.000 description 2
- 108090000387 Endothelin-2 Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108090000371 Esterases Proteins 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 2
- 206010020919 Hypervolaemia Diseases 0.000 description 2
- 208000032382 Ischaemic stroke Diseases 0.000 description 2
- 108010044467 Isoenzymes Proteins 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 208000003773 Meningism Diseases 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 208000019695 Migraine disease Diseases 0.000 description 2
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 2
- 102000003505 Myosin Human genes 0.000 description 2
- 108060008487 Myosin Proteins 0.000 description 2
- 102100035044 Myosin light chain kinase, smooth muscle Human genes 0.000 description 2
- 108010074596 Myosin-Light-Chain Kinase Proteins 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- 206010060860 Neurological symptom Diseases 0.000 description 2
- 101100426589 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) trp-3 gene Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 208000031481 Pathologic Constriction Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108090000030 T-Type Calcium Channels Proteins 0.000 description 2
- 102000003691 T-Type Calcium Channels Human genes 0.000 description 2
- 102000003629 TRPC3 Human genes 0.000 description 2
- 102000003564 TRPC7 Human genes 0.000 description 2
- 101150095096 TRPM2 gene Proteins 0.000 description 2
- 101150037542 Trpc3 gene Proteins 0.000 description 2
- 101150033973 Trpc7 gene Proteins 0.000 description 2
- 208000003443 Unconsciousness Diseases 0.000 description 2
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 2
- 108010004977 Vasopressins Proteins 0.000 description 2
- 102000002852 Vasopressins Human genes 0.000 description 2
- 102100032335 Voltage-dependent calcium channel gamma-8 subunit Human genes 0.000 description 2
- MMWCIQZXVOZEGG-HOZKJCLWSA-N [(1S,2R,3S,4S,5R,6S)-2,3,5-trihydroxy-4,6-diphosphonooxycyclohexyl] dihydrogen phosphate Chemical compound O[C@H]1[C@@H](O)[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](O)[C@H]1OP(O)(O)=O MMWCIQZXVOZEGG-HOZKJCLWSA-N 0.000 description 2
- OHANKWLYFDFHOJ-RFTFGCRPSA-N [(1r,2r,7s,8ar)-1,8a-dimethyl-6-oxo-7-prop-1-en-2-yl-1,2,3,4,7,8-hexahydronaphthalen-2-yl] (z)-3-methylsulfanylprop-2-enoate Chemical compound O=C1[C@H](C(C)=C)C[C@]2(C)[C@@H](C)[C@H](OC(=O)\C=C/SC)CCC2=C1 OHANKWLYFDFHOJ-RFTFGCRPSA-N 0.000 description 2
- 230000036982 action potential Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- 229940072056 alginate Drugs 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 210000003484 anatomy Anatomy 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000001567 anti-fibrinolytic effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 2
- 210000005097 arteria cerebelosa anteroinferior Anatomy 0.000 description 2
- 210000002565 arteriole Anatomy 0.000 description 2
- 210000003403 autonomic nervous system Anatomy 0.000 description 2
- 108091008698 baroreceptors Proteins 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 150000007657 benzothiazepines Chemical class 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 150000001649 bromium compounds Chemical class 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 230000009460 calcium influx Effects 0.000 description 2
- 230000003185 calcium uptake Effects 0.000 description 2
- 210000000269 carotid artery external Anatomy 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 229960004926 chlorobutanol Drugs 0.000 description 2
- 230000002057 chronotropic effect Effects 0.000 description 2
- 230000004186 co-expression Effects 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 230000001010 compromised effect Effects 0.000 description 2
- 238000010968 computed tomography angiography Methods 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 210000000877 corpus callosum Anatomy 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000006196 drop Substances 0.000 description 2
- 239000013583 drug formulation Substances 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 2
- MLFJHYIHIKEBTQ-IYRKOGFYSA-N endothelin 2 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]2CSSC[C@@H](C(N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=3C4=CC=CC=C4NC=3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CSSC1)C1=CNC=N1 MLFJHYIHIKEBTQ-IYRKOGFYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 2
- 229940093471 ethyl oleate Drugs 0.000 description 2
- 210000003414 extremity Anatomy 0.000 description 2
- MEANOSLIBWSCIT-UHFFFAOYSA-K gadolinium trichloride Chemical compound Cl[Gd](Cl)Cl MEANOSLIBWSCIT-UHFFFAOYSA-K 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 230000002008 hemorrhagic effect Effects 0.000 description 2
- 230000003054 hormonal effect Effects 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 230000002102 hyperpolarization Effects 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 239000007972 injectable composition Substances 0.000 description 2
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 150000004694 iodide salts Chemical class 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- ICAKDTKJOYSXGC-UHFFFAOYSA-K lanthanum(iii) chloride Chemical compound Cl[La](Cl)Cl ICAKDTKJOYSXGC-UHFFFAOYSA-K 0.000 description 2
- 125000005647 linker group Chemical group 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 210000003141 lower extremity Anatomy 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 230000036244 malformation Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 230000037323 metabolic rate Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 230000007971 neurological deficit Effects 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 230000003957 neurotransmitter release Effects 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 210000000869 occipital lobe Anatomy 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 210000001152 parietal lobe Anatomy 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 210000003446 pia mater Anatomy 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920002643 polyglutamic acid Polymers 0.000 description 2
- 210000001774 pressoreceptor Anatomy 0.000 description 2
- 210000000063 presynaptic terminal Anatomy 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 230000004952 protein activity Effects 0.000 description 2
- 229940121649 protein inhibitor Drugs 0.000 description 2
- 239000012268 protein inhibitor Substances 0.000 description 2
- GPTFURBXHJWNHR-UHFFFAOYSA-N protopine Chemical compound C1=C2C(=O)CC3=CC=C4OCOC4=C3CN(C)CCC2=CC2=C1OCO2 GPTFURBXHJWNHR-UHFFFAOYSA-N 0.000 description 2
- 208000005333 pulmonary edema Diseases 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000003578 releasing effect Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 208000018316 severe headache Diseases 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 230000036262 stenosis Effects 0.000 description 2
- 208000037804 stenosis Diseases 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 230000002123 temporal effect Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- 102000042565 transient receptor (TC 1.A.4) family Human genes 0.000 description 2
- 108091053409 transient receptor (TC 1.A.4) family Proteins 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 208000019553 vascular disease Diseases 0.000 description 2
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 2
- 229960003726 vasopressin Drugs 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 2
- WVTKBKWTSCPRNU-KYJUHHDHSA-N (+)-Tetrandrine Chemical compound C([C@H]1C=2C=C(C(=CC=2CCN1C)OC)O1)C(C=C2)=CC=C2OC(=C2)C(OC)=CC=C2C[C@@H]2N(C)CCC3=CC(OC)=C(OC)C1=C23 WVTKBKWTSCPRNU-KYJUHHDHSA-N 0.000 description 1
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- AHIFMZUYRNPRJK-MHZLTWQESA-N (1s)-n-(diphenoxyphosphorylmethyl)-2-(4-phenylphenyl)-1-(2h-tetrazol-5-yl)ethanamine Chemical compound C([C@H](NCP(=O)(OC=1C=CC=CC=1)OC=1C=CC=CC=1)C1=NNN=N1)C(C=C1)=CC=C1C1=CC=CC=C1 AHIFMZUYRNPRJK-MHZLTWQESA-N 0.000 description 1
- GTSCNQPMGNAJSH-YHFCJVPQSA-N (2S)-2-[[(2S)-2-[[(4R,7S,10S,16S,19R)-19-[[(3S,6S,9S,12S,15S,21R,26R,29S,32S,35S,38S,41S)-21-[[2-[[(1R,2aR,4S,7S,9aS,10S,12aS,13S,15aS,16S,18aS,19S,22S,25S,28S,31S,34S,37S,40S,43S,46S,52R,57R,60S,63S,66S,69S,72S,75S,81S,84S,87S,90S,93S,96S,99S)-7,63,90-tris(4-aminobutyl)-2a-[[(2S,3S)-2-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-3-methylpentanoyl]amino]-12a-(2-amino-2-oxoethyl)-25-(3-amino-3-oxopropyl)-13-benzyl-16,37,96-tris[(2S)-butan-2-yl]-19,28,46,72-tetrakis(3-carbamimidamidopropyl)-15a,31,43-tris(2-carboxyethyl)-9a,22,60,66-tetrakis[(1R)-1-hydroxyethyl]-40,84-bis(hydroxymethyl)-4,34,99-tris[(4-hydroxyphenyl)methyl]-93-(1H-imidazol-5-ylmethyl)-69,87-dimethyl-81-(2-methylpropyl)-10-(2-methylsulfanylethyl)-1a,2,5,8,8a,11,11a,14,14a,17,17a,20,20a,23,26,29,32,35,38,41,44,47,50,59,62,65,68,71,74,80,83,86,89,92,95,98-hexatriacontaoxo-18a-propan-2-yl-4a,5a,54,55-tetrathia-a,3,6,7a,9,10a,12,13a,15,16a,18,19a,21,24,27,30,33,36,39,42,45,48,51,58,61,64,67,70,73,79,82,85,88,91,94,97-hexatriacontazatricyclo[55.49.14.075,79]icosahectane-52-carbonyl]amino]acetyl]amino]-35-(3-amino-3-oxopropyl)-29-(2-carboxyethyl)-12,32-bis[(1R)-1-hydroxyethyl]-38-[(4-hydroxyphenyl)methyl]-3-(1H-indol-3-ylmethyl)-9-methyl-6-(2-methylsulfanylethyl)-2,5,8,11,14,20,28,31,34,37,40-undecaoxo-23,24-dithia-1,4,7,10,13,19,27,30,33,36,39-undecazatricyclo[39.3.0.015,19]tetratetracontane-26-carbonyl]amino]-16-(4-aminobutyl)-7-(3-carbamimidamidopropyl)-10-(carboxymethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]-4-amino-4-oxobutanoyl]amino]-6-aminohexanoic acid Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@H]1CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CSSC[C@H](NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](Cc3ccccc3)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc3ccc(O)cc3)NC2=O)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(=O)NCC(=O)N[C@H]2CSSC[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@@H]3CCCN3C(=O)[C@H](Cc3c[nH]c4ccccc34)NC(=O)[C@H](CCSC)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H]3CCCN3C2=O)[C@@H](C)O)[C@@H](C)O)C(=O)N[C@H]2CSSC[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCCN)NC2=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC1=O)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O GTSCNQPMGNAJSH-YHFCJVPQSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- CRUVAUSVWLATAE-ZDUSSCGKSA-N (2s)-3-dibenzofuran-3-yl-2-(phosphonomethylamino)propanoic acid Chemical compound C1=CC=C2C3=CC=C(C[C@@H](C(=O)O)NCP(O)(O)=O)C=C3OC2=C1 CRUVAUSVWLATAE-ZDUSSCGKSA-N 0.000 description 1
- CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 1
- ZFLWDHHVRRZMEI-CYBMUJFWSA-N (4R)-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylic acid methyl ester Chemical compound COC(=O)C1=C(C)NC(C)=C([N+]([O-])=O)[C@@H]1C1=CC=CC=C1C(F)(F)F ZFLWDHHVRRZMEI-CYBMUJFWSA-N 0.000 description 1
- ZWTDXYUDJYDHJR-UHFFFAOYSA-N (E)-1-(2,4-dihydroxyphenyl)-3-(2,4-dihydroxyphenyl)-2-propen-1-one Natural products OC1=CC(O)=CC=C1C=CC(=O)C1=CC=C(O)C=C1O ZWTDXYUDJYDHJR-UHFFFAOYSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- UUDAMDVQRQNNHZ-UHFFFAOYSA-N (S)-AMPA Chemical compound CC=1ONC(=O)C=1CC(N)C(O)=O UUDAMDVQRQNNHZ-UHFFFAOYSA-N 0.000 description 1
- NCUVPPXIIPVXMO-UHFFFAOYSA-N 1,2-benzothiazepine;calcium Chemical compound [Ca].S1N=CC=CC2=CC=CC=C12 NCUVPPXIIPVXMO-UHFFFAOYSA-N 0.000 description 1
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical class CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
- VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical class CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 description 1
- 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
- WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical class BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
- BVABFIZTUSTDDW-UHFFFAOYSA-N 5h-1,2-benzothiazepin-4-one Chemical compound S1N=CC(=O)CC2=CC=CC=C21 BVABFIZTUSTDDW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 206010050013 Abulia Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102100026024 Acyl-coenzyme A synthetase ACSM3, mitochondrial Human genes 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 241000238898 Agelenopsis aperta Species 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 102400000345 Angiotensin-2 Human genes 0.000 description 1
- 101800000733 Angiotensin-2 Proteins 0.000 description 1
- 102000008102 Ankyrins Human genes 0.000 description 1
- 108010049777 Ankyrins Proteins 0.000 description 1
- 206010002660 Anoxia Diseases 0.000 description 1
- 241000976983 Anoxia Species 0.000 description 1
- 102000003669 Antiporters Human genes 0.000 description 1
- 108090000084 Antiporters Proteins 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 206010003162 Arterial injury Diseases 0.000 description 1
- 206010003225 Arteriospasm coronary Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- 206010003662 Atrial flutter Diseases 0.000 description 1
- 101800001288 Atrial natriuretic factor Proteins 0.000 description 1
- 102400001282 Atrial natriuretic peptide Human genes 0.000 description 1
- 101800001890 Atrial natriuretic peptide Proteins 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 208000019838 Blood disease Diseases 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- 102400000967 Bradykinin Human genes 0.000 description 1
- 206010006126 Brain herniation Diseases 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 101710202985 Calciseptin Proteins 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000020446 Cardiac disease Diseases 0.000 description 1
- 206010007558 Cardiac failure chronic Diseases 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
- 206010008138 Cerebral venous thrombosis Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 208000003890 Coronary Vasospasm Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 208000019736 Cranial nerve disease Diseases 0.000 description 1
- 102000004420 Creatine Kinase Human genes 0.000 description 1
- 108010042126 Creatine kinase Proteins 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 206010051055 Deep vein thrombosis Diseases 0.000 description 1
- 241000272023 Dendroaspis polylepis Species 0.000 description 1
- 241000272019 Dendroaspis polylepis polylepis Species 0.000 description 1
- 101000723297 Dendroaspis polylepis polylepis Calciseptin Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 241001269524 Dura Species 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 206010014418 Electrolyte imbalance Diseases 0.000 description 1
- 208000007530 Essential hypertension Diseases 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 208000031969 Eye Hemorrhage Diseases 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 102100035233 Furin Human genes 0.000 description 1
- 108090001126 Furin Proteins 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000018899 Glutamate Receptors Human genes 0.000 description 1
- 108010027915 Glutamate Receptors Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
- 206010018852 Haematoma Diseases 0.000 description 1
- 206010059484 Haemodilution Diseases 0.000 description 1
- 206010018985 Haemorrhage intracranial Diseases 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 208000010271 Heart Block Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 206010019468 Hemiplegia Diseases 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 208000016988 Hemorrhagic Stroke Diseases 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 101000932850 Homo sapiens Voltage-dependent L-type calcium channel subunit beta-1 Proteins 0.000 description 1
- 101000983956 Homo sapiens Voltage-dependent L-type calcium channel subunit beta-2 Proteins 0.000 description 1
- 101000983936 Homo sapiens Voltage-dependent L-type calcium channel subunit beta-3 Proteins 0.000 description 1
- 101000983947 Homo sapiens Voltage-dependent L-type calcium channel subunit beta-4 Proteins 0.000 description 1
- 101000910759 Homo sapiens Voltage-dependent calcium channel gamma-1 subunit Proteins 0.000 description 1
- 101000910758 Homo sapiens Voltage-dependent calcium channel gamma-2 subunit Proteins 0.000 description 1
- 101000910745 Homo sapiens Voltage-dependent calcium channel gamma-3 subunit Proteins 0.000 description 1
- 101000910748 Homo sapiens Voltage-dependent calcium channel gamma-4 subunit Proteins 0.000 description 1
- 101000868383 Homo sapiens Voltage-dependent calcium channel gamma-5 subunit Proteins 0.000 description 1
- 101000868391 Homo sapiens Voltage-dependent calcium channel gamma-6 subunit Proteins 0.000 description 1
- 101000868398 Homo sapiens Voltage-dependent calcium channel gamma-7 subunit Proteins 0.000 description 1
- 101000868545 Homo sapiens Voltage-dependent calcium channel gamma-8 subunit Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- 206010021137 Hypovolaemia Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- 208000008574 Intracranial Hemorrhages Diseases 0.000 description 1
- 206010022773 Intracranial pressure increased Diseases 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 206010024264 Lethargy Diseases 0.000 description 1
- 208000008930 Low Back Pain Diseases 0.000 description 1
- 208000004852 Lung Injury Diseases 0.000 description 1
- 108090000362 Lymphotoxin-beta Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- DUGOZIWVEXMGBE-UHFFFAOYSA-N Methylphenidate Chemical compound C=1C=CC=CC=1C(C(=O)OC)C1CCCCN1 DUGOZIWVEXMGBE-UHFFFAOYSA-N 0.000 description 1
- HBNPJJILLOYFJU-VMPREFPWSA-N Mibefradil Chemical compound C1CC2=CC(F)=CC=C2[C@H](C(C)C)[C@@]1(OC(=O)COC)CCN(C)CCCC1=NC2=CC=CC=C2N1 HBNPJJILLOYFJU-VMPREFPWSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241001024304 Mino Species 0.000 description 1
- 102000011131 Myosin-Light-Chain Phosphatase Human genes 0.000 description 1
- 108010037801 Myosin-Light-Chain Phosphatase Proteins 0.000 description 1
- ZYFVLHYHXNFROE-KRWDZBQOSA-N N'-[(5S)-1-(hydroxyamino)-1-oxononan-5-yl]-N-phenylhexanediamide Chemical compound ONC(CCC[C@H](CCCC)NC(CCCCC(=O)NC1=CC=CC=C1)=O)=O ZYFVLHYHXNFROE-KRWDZBQOSA-N 0.000 description 1
- YQHMWTPYORBCMF-UHFFFAOYSA-N Naringenin chalcone Natural products C1=CC(O)=CC=C1C=CC(=O)C1=C(O)C=C(O)C=C1O YQHMWTPYORBCMF-UHFFFAOYSA-N 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 208000008457 Neurologic Manifestations Diseases 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102400000050 Oxytocin Human genes 0.000 description 1
- XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 description 1
- 101800000989 Oxytocin Proteins 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 206010033425 Pain in extremity Diseases 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 206010034960 Photophobia Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920001305 Poly(isodecyl(meth)acrylate) Polymers 0.000 description 1
- 229920002319 Poly(methyl acrylate) Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 201000001068 Prinzmetal angina Diseases 0.000 description 1
- 102100024819 Prolactin Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- GTRPODKMSBFDOI-UHFFFAOYSA-N Protopine Natural products CN1Cc2c3OCOc3ccc2C4C1Cc5cc6OCOc6cc5C4=O GTRPODKMSBFDOI-UHFFFAOYSA-N 0.000 description 1
- ZAALQOFZFANFTF-UHFFFAOYSA-N Pseudoprotipine Natural products C1=C2C(=O)CC3=CC=4OCOC=4C=C3CN(C)CCC2=CC2=C1OCO2 ZAALQOFZFANFTF-UHFFFAOYSA-N 0.000 description 1
- 102000002298 Purinergic P2Y Receptors Human genes 0.000 description 1
- 108010000818 Purinergic P2Y Receptors Proteins 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 108010027023 Q-Type Calcium Channels Proteins 0.000 description 1
- 102000001424 Ryanodine receptors Human genes 0.000 description 1
- VWBBKDOYFZXORP-UHFFFAOYSA-N S-Petasin Natural products CC1C(CCC2=CC(=O)C(CC12C)C(=C)C)OC(=O)C=C/CS VWBBKDOYFZXORP-UHFFFAOYSA-N 0.000 description 1
- 102000000395 SH3 domains Human genes 0.000 description 1
- 108050008861 SH3 domains Proteins 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 208000028979 Skull fracture Diseases 0.000 description 1
- 208000032140 Sleepiness Diseases 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 208000007718 Stable Angina Diseases 0.000 description 1
- 229920002472 Starch Chemical class 0.000 description 1
- 208000010513 Stupor Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 208000002847 Surgical Wound Diseases 0.000 description 1
- 102000003673 Symporters Human genes 0.000 description 1
- 108090000088 Symporters Proteins 0.000 description 1
- 206010042957 Systolic hypertension Diseases 0.000 description 1
- IBUAONLWVYWMIS-UHFFFAOYSA-N TMC-66 Natural products O=C1C2=C(O)C=CC=C2C(=O)C2=C1C=C1CCC(C=C3CC4(N(C(=O)C3=C3O)C(CO4)C(O)=O)C)=C3C1=C2O IBUAONLWVYWMIS-UHFFFAOYSA-N 0.000 description 1
- 101150006914 TRP1 gene Proteins 0.000 description 1
- 102000011040 TRPV Cation Channels Human genes 0.000 description 1
- 108010062740 TRPV Cation Channels Proteins 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 0.000 description 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 1
- IVTVGDXNLFLDRM-HNNXBMFYSA-N Tomudex Chemical compound C=1C=C2NC(C)=NC(=O)C2=CC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)S1 IVTVGDXNLFLDRM-HNNXBMFYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 206010069363 Traumatic lung injury Diseases 0.000 description 1
- 102000013534 Troponin C Human genes 0.000 description 1
- LVTKHGUGBGNBPL-UHFFFAOYSA-N Trp-P-1 Chemical compound N1C2=CC=CC=C2C2=C1C(C)=C(N)N=C2C LVTKHGUGBGNBPL-UHFFFAOYSA-N 0.000 description 1
- 208000009443 Vascular Malformations Diseases 0.000 description 1
- 206010047050 Vascular anomaly Diseases 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 208000034698 Vitreous haemorrhage Diseases 0.000 description 1
- 102000016913 Voltage-Gated Sodium Channels Human genes 0.000 description 1
- 108010053752 Voltage-Gated Sodium Channels Proteins 0.000 description 1
- 102100025568 Voltage-dependent L-type calcium channel subunit beta-1 Human genes 0.000 description 1
- 102100025807 Voltage-dependent L-type calcium channel subunit beta-2 Human genes 0.000 description 1
- 102100025838 Voltage-dependent L-type calcium channel subunit beta-3 Human genes 0.000 description 1
- 102100025836 Voltage-dependent L-type calcium channel subunit beta-4 Human genes 0.000 description 1
- 102100024142 Voltage-dependent calcium channel gamma-1 subunit Human genes 0.000 description 1
- 102100024141 Voltage-dependent calcium channel gamma-2 subunit Human genes 0.000 description 1
- 102100024138 Voltage-dependent calcium channel gamma-3 subunit Human genes 0.000 description 1
- 102100024143 Voltage-dependent calcium channel gamma-4 subunit Human genes 0.000 description 1
- 102100032867 Voltage-dependent calcium channel gamma-5 subunit Human genes 0.000 description 1
- 102100032869 Voltage-dependent calcium channel gamma-7 subunit Human genes 0.000 description 1
- 101000998548 Yersinia ruckeri Alkaline proteinase inhibitor Proteins 0.000 description 1
- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 description 1
- DOQPXTMNIUCOSY-UHFFFAOYSA-N [4-cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl]-[2-(3,4-dimethoxyphenyl)ethyl]-methylazanium;chloride Chemical compound [H+].[Cl-].C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 DOQPXTMNIUCOSY-UHFFFAOYSA-N 0.000 description 1
- UUMKQZVEZSXWBY-HNNXBMFYSA-N [[(1s)-2-(4-phenylphenyl)-1-(2h-tetrazol-5-yl)ethyl]amino]methylphosphonic acid Chemical compound C([C@H](NCP(O)(=O)O)C1=NNN=N1)C(C=C1)=CC=C1C1=CC=CC=C1 UUMKQZVEZSXWBY-HNNXBMFYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 206010000269 abscess Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 229920006397 acrylic thermoplastic Polymers 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 229950006323 angiotensin ii Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000007953 anoxia Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229940053200 antiepileptics fatty acid derivative Drugs 0.000 description 1
- 239000000504 antifibrinolytic agent Substances 0.000 description 1
- 229940082620 antifibrinolytics Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 201000007201 aphasia Diseases 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000008321 arterial blood flow Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000001042 autoregulative effect Effects 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 238000009412 basement excavation Methods 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- 235000012216 bentonite Nutrition 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000000227 bioadhesive Substances 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 231100001015 blood dyscrasias Toxicity 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- 229960005069 calcium Drugs 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 230000008061 calcium-channel-blocking effect Effects 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- VNWKTOKETHGBQD-YPZZEJLDSA-N carbane Chemical compound [10CH4] VNWKTOKETHGBQD-YPZZEJLDSA-N 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 210000001168 carotid artery common Anatomy 0.000 description 1
- NSQLIUXCMFBZME-MPVJKSABSA-N carperitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 NSQLIUXCMFBZME-MPVJKSABSA-N 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 210000000711 cavernous sinus Anatomy 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Chemical class 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Chemical class 0.000 description 1
- 210000000782 cerebellar granule cell Anatomy 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 238000002585 cerebral angiography Methods 0.000 description 1
- 210000004289 cerebral ventricle Anatomy 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol group Chemical group [C@@H]1(CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)[C@H](C)CCCC(C)C HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000006854 communication Effects 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 201000011634 coronary artery vasospasm Diseases 0.000 description 1
- 238000007428 craniotomy Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229960003624 creatine Drugs 0.000 description 1
- 239000006046 creatine Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
- 239000000850 decongestant Substances 0.000 description 1
- 229940124581 decongestants Drugs 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000030609 dephosphorylation Effects 0.000 description 1
- 238000006209 dephosphorylation reaction Methods 0.000 description 1
- 230000002999 depolarising effect Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 230000015155 detection of stimulus involved in sensory perception Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- SGTNSNPWRIOYBX-HHHXNRCGSA-N dexverapamil Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCC[C@@](C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-HHHXNRCGSA-N 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 150000001982 diacylglycerols Chemical class 0.000 description 1
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- 210000002451 diencephalon Anatomy 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 229940127292 dihydropyridine calcium channel blocker Drugs 0.000 description 1
- 239000002866 dihydropyridine calcium channel blocker Substances 0.000 description 1
- CHWPMFMUQATVNK-ARYYTZDLSA-N dihydrosporogen AO-1 Natural products O[C@H]1[C@]2(C(C)=C)O[C@@H]2[C@]2(C)[C@@H](C)[C@H](O)CCC2=C1 CHWPMFMUQATVNK-ARYYTZDLSA-N 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- GAFRWLVTHPVQGK-UHFFFAOYSA-N dipentyl sulfate Chemical class CCCCCOS(=O)(=O)OCCCCC GAFRWLVTHPVQGK-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000009552 doppler ultrasonography Methods 0.000 description 1
- 230000001091 dromotropic effect Effects 0.000 description 1
- 238000009513 drug distribution Methods 0.000 description 1
- 210000001951 dura mater Anatomy 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000008151 electrolyte solution Substances 0.000 description 1
- 230000005672 electromagnetic field Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000003890 endocrine cell Anatomy 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 1
- 229960001123 epoprostenol Drugs 0.000 description 1
- 229930013356 epothilone Natural products 0.000 description 1
- 150000003883 epothilone derivatives Chemical class 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000013265 extended release Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000004424 eye movement Effects 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- RZTAMFZIAATZDJ-UHFFFAOYSA-N felodipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-UHFFFAOYSA-N 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000002532 foramen magnum Anatomy 0.000 description 1
- PGBHMTALBVVCIT-VCIWKGPPSA-N framycetin Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CN)O2)N)O[C@@H]1CO PGBHMTALBVVCIT-VCIWKGPPSA-N 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229960002870 gabapentin Drugs 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 239000012213 gelatinous substance Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 210000001905 globus pallidus Anatomy 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- SYUXAJSOZXEFPP-UHFFFAOYSA-N glutin Natural products COc1c(O)cc2OC(=CC(=O)c2c1O)c3ccccc3OC4OC(CO)C(O)C(O)C4O SYUXAJSOZXEFPP-UHFFFAOYSA-N 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 210000004013 groin Anatomy 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 238000005534 hematocrit Methods 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 102000040854 high voltage-gated calcium channel activity Human genes 0.000 description 1
- 108091092197 high voltage-gated calcium channel activity Proteins 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000002433 hydrophilic molecules Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000000960 hypophysis hormone Substances 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 210000004020 intracellular membrane Anatomy 0.000 description 1
- 201000009941 intracranial hypertension Diseases 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 230000003447 ipsilateral effect Effects 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- WVTKBKWTSCPRNU-XZWHSSHBSA-N isotetrandrine Chemical compound C([C@H]1C=2C=C(C(=CC=2CCN1C)OC)O1)C(C=C2)=CC=C2OC(=C2)C(OC)=CC=C2C[C@H]2N(C)CCC3=CC(OC)=C(OC)C1=C23 WVTKBKWTSCPRNU-XZWHSSHBSA-N 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000002197 limbic effect Effects 0.000 description 1
- 239000008206 lipophilic material Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 231100000515 lung injury Toxicity 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 150000002680 magnesium Chemical class 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 210000004779 membrane envelope Anatomy 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 210000002418 meninge Anatomy 0.000 description 1
- 230000009245 menopause Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
- ZMJUWFXCWLDAKQ-WZJLIZBTSA-N methyl 4-[[(3r,4s,5s,6r)-4,5-dihydroxy-7-[[4-(hydroxymethyl)phenyl]methyl]-1,1-dioxo-3,6-bis(phenoxymethyl)-1,2,7-thiadiazepan-2-yl]methyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CN1S(=O)(=O)N(CC=2C=CC(CO)=CC=2)[C@H](COC=2C=CC=CC=2)[C@H](O)[C@@H](O)[C@H]1COC1=CC=CC=C1 ZMJUWFXCWLDAKQ-WZJLIZBTSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960001344 methylphenidate Drugs 0.000 description 1
- 229960004438 mibefradil Drugs 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 210000003632 microfilament Anatomy 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 210000000107 myocyte Anatomy 0.000 description 1
- 210000001087 myotubule Anatomy 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 229940053050 neomycin sulfate Drugs 0.000 description 1
- 210000001640 nerve ending Anatomy 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 230000001272 neurogenic effect Effects 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000010353 neuronal integration Effects 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- UIAGMCDKSXEBJQ-UHFFFAOYSA-N nimodipine Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-UHFFFAOYSA-N 0.000 description 1
- PVHUJELLJLJGLN-UHFFFAOYSA-N nitrendipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC([N+]([O-])=O)=C1 PVHUJELLJLJGLN-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 230000035761 normovolemia Effects 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 210000002589 oculomotor nerve Anatomy 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 210000004409 osteocyte Anatomy 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000036284 oxygen consumption Effects 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 description 1
- 229960001723 oxytocin Drugs 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 230000001936 parietal effect Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 150000004633 phorbol derivatives Chemical class 0.000 description 1
- 239000002644 phorbol ester Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001490 poly(butyl methacrylate) polymer Polymers 0.000 description 1
- 229920000212 poly(isobutyl acrylate) Polymers 0.000 description 1
- 229920000205 poly(isobutyl methacrylate) Polymers 0.000 description 1
- 229920000196 poly(lauryl methacrylate) Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920000184 poly(octadecyl acrylate) Polymers 0.000 description 1
- 229920002463 poly(p-dioxanone) polymer Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 239000000622 polydioxanone Substances 0.000 description 1
- 229920000129 polyhexylmethacrylate Polymers 0.000 description 1
- 229920000197 polyisopropyl acrylate Polymers 0.000 description 1
- 238000012667 polymer degradation Methods 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920000182 polyphenyl methacrylate Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 210000003240 portal vein Anatomy 0.000 description 1
- 230000012495 positive regulation of renal sodium excretion Effects 0.000 description 1
- 208000028173 post-traumatic stress disease Diseases 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229960001233 pregabalin Drugs 0.000 description 1
- AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 108010072272 proendothelin 1 Proteins 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 description 1
- 229960003908 pseudoephedrine Drugs 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 230000008704 pulmonary vasodilation Effects 0.000 description 1
- 210000001747 pupil Anatomy 0.000 description 1
- 230000001179 pupillary effect Effects 0.000 description 1
- 210000000449 purkinje cell Anatomy 0.000 description 1
- 210000003742 purkinje fiber Anatomy 0.000 description 1
- 210000002637 putamen Anatomy 0.000 description 1
- 210000002763 pyramidal cell Anatomy 0.000 description 1
- WVTKBKWTSCPRNU-UHFFFAOYSA-N rac-Tetrandrin Natural products O1C(C(=CC=2CCN3C)OC)=CC=2C3CC(C=C2)=CC=C2OC(=C2)C(OC)=CC=C2CC2N(C)CCC3=CC(OC)=C(OC)C1=C23 WVTKBKWTSCPRNU-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000029865 regulation of blood pressure Effects 0.000 description 1
- 230000004648 relaxation of smooth muscle Effects 0.000 description 1
- 230000036454 renin-angiotensin system Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000036387 respiratory rate Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000036390 resting membrane potential Effects 0.000 description 1
- 210000003994 retinal ganglion cell Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 108091052345 ryanodine receptor (TC 1.A.3.1) family Proteins 0.000 description 1
- 210000002235 sarcomere Anatomy 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 230000037321 sleepiness Effects 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 238000012732 spatial analysis Methods 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 210000002948 striated muscle cell Anatomy 0.000 description 1
- 210000003270 subclavian artery Anatomy 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000007460 surgical drainage Methods 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000009182 swimming Effects 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 210000003478 temporal lobe Anatomy 0.000 description 1
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000024033 toxin binding Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 210000004231 tunica media Anatomy 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000006442 vascular tone Effects 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000003156 vasculitic effect Effects 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 230000002455 vasospastic effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000002435 venom Substances 0.000 description 1
- 231100000611 venom Toxicity 0.000 description 1
- 210000001048 venom Anatomy 0.000 description 1
- 210000005111 ventral hippocampus Anatomy 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 210000004127 vitreous body Anatomy 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
- 230000007279 water homeostasis Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0085—Brain, e.g. brain implants; Spinal cord
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- General Chemical & Material Sciences (AREA)
- Psychology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Inorganic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2013203192A AU2013203192B2 (en) | 2007-06-11 | 2013-04-09 | A drug delivery system for the prevention of cerebral vasospasm |
| AU2016201681A AU2016201681B2 (en) | 2007-06-11 | 2016-03-16 | A drug delivery system for the prevention of cerebral vasospasm |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US94312407P | 2007-06-11 | 2007-06-11 | |
| US60/943,124 | 2007-06-11 | ||
| US97690207P | 2007-10-29 | 2007-10-29 | |
| US60/976,902 | 2007-10-29 | ||
| PCT/US2008/066576 WO2008154585A1 (en) | 2007-06-11 | 2008-06-11 | A drug delivery system for the prevention of cerebral vasospasm |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2013203192A Division AU2013203192B2 (en) | 2007-06-11 | 2013-04-09 | A drug delivery system for the prevention of cerebral vasospasm |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| AU2008261668A1 AU2008261668A1 (en) | 2008-12-18 |
| AU2008261668B2 AU2008261668B2 (en) | 2013-08-29 |
| AU2008261668C1 true AU2008261668C1 (en) | 2014-01-16 |
Family
ID=40096090
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2008261668A Ceased AU2008261668C1 (en) | 2007-06-11 | 2008-06-11 | A drug delivery system for the prevention of cerebral vasospasm |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US8303974B2 (https=) |
| EP (1) | EP2164497B1 (https=) |
| JP (1) | JP5576790B2 (https=) |
| KR (3) | KR101607244B1 (https=) |
| CN (3) | CN101873858B (https=) |
| AU (1) | AU2008261668C1 (https=) |
| CA (1) | CA2690600C (https=) |
| IL (1) | IL202647A (https=) |
| NZ (2) | NZ581836A (https=) |
| WO (1) | WO2008154585A1 (https=) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8303974B2 (en) * | 2007-06-11 | 2012-11-06 | Edge Therapeutics, Inc. | Drug delivery system for the prevention of cerebral vasospasm |
| US10092524B2 (en) | 2008-06-11 | 2018-10-09 | Edge Therapeutics, Inc. | Compositions and their use to treat complications of aneurysmal subarachnoid hemorrhage |
| US8252302B2 (en) * | 2007-06-11 | 2012-08-28 | Edge Therapeutics, Inc. | Methods and compositions to treat hemorrhagic conditions of the brain |
| EP2308478A1 (en) | 2009-10-06 | 2011-04-13 | Abbott GmbH & Co. KG | Delivery system for sustained release of a calcium-channel blocking agent |
| EP2627173B2 (en) | 2010-10-12 | 2018-07-04 | Chiesi Farmaceutici S.p.A. | Clevidipine emulsion formulations containing antimicrobial agents |
| US8658676B2 (en) * | 2010-10-12 | 2014-02-25 | The Medicines Company | Clevidipine emulsion formulations containing antimicrobial agents |
| EP2672983B1 (en) * | 2011-02-11 | 2017-04-19 | Edge Therapeutics, Inc. | Compositions and methods for improving prognosis of a human with subarachnoid hemorrhage |
| HK1198933A1 (en) * | 2011-04-05 | 2015-06-19 | Edge Therapeutics | Intraventricular drug delivery system for improving outcome after a brain injury affecting cerebral blood flow |
| CN102416013A (zh) * | 2011-12-30 | 2012-04-18 | 湖南九典制药有限公司 | 西尼地平的新用途 |
| US9399019B2 (en) * | 2012-05-09 | 2016-07-26 | Evonik Corporation | Polymorph compositions, methods of making, and uses thereof |
| WO2014165023A1 (en) | 2013-03-12 | 2014-10-09 | Carnegie Mellon University | Coated vaso-occclusive device for treatment of aneurysms |
| CN103211812A (zh) * | 2013-04-02 | 2013-07-24 | 苏州大学附属第一医院 | Skf96365在治疗蛛网膜下腔出血后发生的脑血管痉挛的应用 |
| US10403395B2 (en) * | 2013-10-14 | 2019-09-03 | SecondOpinionExpert, Inc. | Method and apparatus for generating objective medical second opinion |
| CA2975447C (en) * | 2015-01-30 | 2021-02-23 | The Regents Of The University Of California | Spinal subpial gene delivery system |
| KR20180021741A (ko) * | 2015-05-29 | 2018-03-05 | 에쥐 세라피틱스, 인코포레이티드 | 시각 손실을 감소시키기 위한 조성물 및 방법 |
| US10695400B2 (en) * | 2015-08-03 | 2020-06-30 | Enb Therapeutics, Inc. | Compositions and methods for treating cancers associated with ETBR activation |
| AU2018300080B2 (en) | 2017-07-11 | 2024-09-19 | Sustained Nano Systems Llc | Hypercompressed pharmaceutical formulations |
| AU2019206652B2 (en) | 2018-01-12 | 2024-11-14 | Enb Therapeutics, Inc. | Deuterated compounds, compositions, and methods for treating cancers associated with ETBR activation |
| US20200163947A1 (en) * | 2018-11-02 | 2020-05-28 | Nortic Holdings Inc. | Methods of treatment using nimodipine parenteral formulations |
| US11103142B2 (en) | 2019-04-02 | 2021-08-31 | Tencent America LLC | System and method for predicting vertebral artery dissection |
| US20200315547A1 (en) * | 2019-04-02 | 2020-10-08 | Tencent America LLC | Vertebral artery dissection risk evaluation method, computer device, and storage medium |
| JP7716076B2 (ja) * | 2021-02-04 | 2025-07-31 | 学校法人産業医科大学 | 血管内穿孔によるくも膜下出血モデルの血腫を可視化する方法 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5993855A (en) * | 1995-09-18 | 1999-11-30 | Shiseido Company, Ltd. | Delayed drug-releasing microspheres |
| WO2006084005A2 (en) * | 2005-02-02 | 2006-08-10 | University Of Vermont And State Agricultural College | Emergence of a r-type ca2+channel(cav2.3) contributes to cerebral artery constriction following subarachnoid hemorrhage |
| US20060205733A1 (en) * | 2004-08-26 | 2006-09-14 | Encysive Pharmaceuticals | Endothelin a receptor antagonists in combination with phosphodiesterase 5 inhibitors and uses thereof |
| US20060217340A1 (en) * | 2005-03-23 | 2006-09-28 | University Of Vermont And State Agricultural College | Methods and products for treating hypertension by modulation of TRPC3 channel activity |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5650489A (en) | 1990-07-02 | 1997-07-22 | The Arizona Board Of Regents | Random bio-oligomer library, a method of synthesis thereof, and a method of use thereof |
| WO1995018972A1 (en) | 1994-01-05 | 1995-07-13 | Arqule, Inc. | Systematic modular production of aminimide- and oxazolone-based molecules having selected properties |
| US5712171A (en) | 1995-01-20 | 1998-01-27 | Arqule, Inc. | Method of generating a plurality of chemical compounds in a spatially arranged array |
| DE69735057T2 (de) | 1996-03-12 | 2006-08-31 | PG-TXL Co., L.P., Houston | Wasserlösliche paclitaxel-prodrogen |
| US6123956A (en) | 1997-07-10 | 2000-09-26 | Keith Baker | Methods for universally distributing therapeutic agents to the brain |
| US6284283B1 (en) * | 1999-10-21 | 2001-09-04 | Alkermes Controlled Therapeutics, Inc. | Method of producing sub-micron particles of biologically active agents and uses thereof |
| JP2002003406A (ja) * | 2000-06-21 | 2002-01-09 | Sankyo Co Ltd | 脳血管攣縮予防製剤 |
| US20030032676A1 (en) * | 2001-08-09 | 2003-02-13 | Kimelberg Harold K. | Drugs for treatment of cerebral injury and methods of use thereof |
| US20040224030A1 (en) * | 2003-05-06 | 2004-11-11 | Shastri Venkatram R. | Microsphere delivery systems |
| WO2005009357A2 (en) * | 2003-07-23 | 2005-02-03 | Pr Pharmaceuticals, Inc. | Controlled release compositions |
| CN1480128A (zh) * | 2003-08-06 | 2004-03-10 | 北京扬新科技有限公司 | 一种透明、隐形的外用药物制剂 |
| BRPI0414907A (pt) * | 2003-09-30 | 2006-11-07 | Acusphere Inc | formulações farmacêuticas com liberação sustentada injetáveis, orais ou tópicas |
| US8303974B2 (en) * | 2007-06-11 | 2012-11-06 | Edge Therapeutics, Inc. | Drug delivery system for the prevention of cerebral vasospasm |
-
2008
- 2008-06-11 US US12/137,320 patent/US8303974B2/en not_active Expired - Fee Related
- 2008-06-11 WO PCT/US2008/066576 patent/WO2008154585A1/en not_active Ceased
- 2008-06-11 EP EP08770723.8A patent/EP2164497B1/en not_active Not-in-force
- 2008-06-11 CN CN200880101555.8A patent/CN101873858B/zh not_active Expired - Fee Related
- 2008-06-11 CN CN201510300314.8A patent/CN105055300A/zh active Pending
- 2008-06-11 NZ NZ581836A patent/NZ581836A/en not_active IP Right Cessation
- 2008-06-11 KR KR1020147036026A patent/KR101607244B1/ko not_active Expired - Fee Related
- 2008-06-11 CA CA2690600A patent/CA2690600C/en not_active Expired - Fee Related
- 2008-06-11 KR KR1020107000554A patent/KR101554250B1/ko not_active Expired - Fee Related
- 2008-06-11 NZ NZ599430A patent/NZ599430A/en not_active IP Right Cessation
- 2008-06-11 JP JP2010512324A patent/JP5576790B2/ja not_active Expired - Fee Related
- 2008-06-11 AU AU2008261668A patent/AU2008261668C1/en not_active Ceased
- 2008-06-11 CN CN201610281218.8A patent/CN105963242A/zh active Pending
- 2008-06-11 KR KR1020157012919A patent/KR101554258B1/ko not_active Expired - Fee Related
-
2009
- 2009-12-10 IL IL202647A patent/IL202647A/en active IP Right Grant
-
2012
- 2012-07-22 US US13/555,182 patent/US20130022660A1/en not_active Abandoned
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5993855A (en) * | 1995-09-18 | 1999-11-30 | Shiseido Company, Ltd. | Delayed drug-releasing microspheres |
| US20060205733A1 (en) * | 2004-08-26 | 2006-09-14 | Encysive Pharmaceuticals | Endothelin a receptor antagonists in combination with phosphodiesterase 5 inhibitors and uses thereof |
| WO2006084005A2 (en) * | 2005-02-02 | 2006-08-10 | University Of Vermont And State Agricultural College | Emergence of a r-type ca2+channel(cav2.3) contributes to cerebral artery constriction following subarachnoid hemorrhage |
| US20060229269A1 (en) * | 2005-02-02 | 2006-10-12 | University Of Vermont And State Agricultural College | Emergence of a R-type Ca²+ channel (Cav 2.3) contributes to cerebral artery constriction following subarachnoid hemorrhage |
| US20060217340A1 (en) * | 2005-03-23 | 2006-09-28 | University Of Vermont And State Agricultural College | Methods and products for treating hypertension by modulation of TRPC3 channel activity |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101873858A (zh) | 2010-10-27 |
| CA2690600A1 (en) | 2008-12-18 |
| NZ581836A (en) | 2012-07-27 |
| JP5576790B2 (ja) | 2014-08-20 |
| EP2164497A4 (en) | 2013-05-29 |
| KR20100055385A (ko) | 2010-05-26 |
| KR101554258B1 (ko) | 2015-09-18 |
| US20080305147A1 (en) | 2008-12-11 |
| JP2010529205A (ja) | 2010-08-26 |
| KR101554250B1 (ko) | 2015-09-18 |
| US20130022660A1 (en) | 2013-01-24 |
| AU2008261668A1 (en) | 2008-12-18 |
| CN105055300A (zh) | 2015-11-18 |
| US8303974B2 (en) | 2012-11-06 |
| EP2164497A1 (en) | 2010-03-24 |
| WO2008154585A1 (en) | 2008-12-18 |
| KR20150061031A (ko) | 2015-06-03 |
| CA2690600C (en) | 2016-10-11 |
| AU2008261668B2 (en) | 2013-08-29 |
| CN101873858B (zh) | 2016-05-25 |
| NZ599430A (en) | 2014-03-28 |
| CN105963242A (zh) | 2016-09-28 |
| IL202647A0 (en) | 2010-06-30 |
| KR101607244B1 (ko) | 2016-03-30 |
| EP2164497B1 (en) | 2018-08-15 |
| KR20150015514A (ko) | 2015-02-10 |
| IL202647A (en) | 2015-02-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2008261668C1 (en) | A drug delivery system for the prevention of cerebral vasospasm | |
| EP2694133B1 (en) | Intraventricular drug delivery system for improving outcome after a brain injury affecting cerebral blood flow | |
| RU2597791C2 (ru) | Композиции и способы улучшения прогноза человека с субарахноидальным кровоизлиянием | |
| AU2016201681B2 (en) | A drug delivery system for the prevention of cerebral vasospasm | |
| AU2013203192B2 (en) | A drug delivery system for the prevention of cerebral vasospasm | |
| CA2826890A1 (en) | Compositions and methods for improving prognosis of a human with subarachnoid hemorrhage | |
| HK1229243A1 (en) | A drug delivery system for the prevention of cerebral vasospasm | |
| NZ613970B2 (en) | Compositions and methods for improving prognosis of a human with subarachnoid hemorrhage | |
| NZ727856B2 (en) | Intraventricular drug delivery system for improving outcome after a brain injury affecting cerebral blood flow | |
| NZ714032B2 (en) | Intraventricular drug delivery system for improving outcome after a brain injury affecting cerebral blood flow |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PC1 | Assignment before grant (sect. 113) |
Owner name: EDGE THERAPEUTICS INC. Free format text: FORMER APPLICANT(S): MACDONALD, R.; LEUTHNER, BRIAN |
|
| DA2 | Applications for amendment section 104 |
Free format text: THE NATURE OF THE AMENDMENT IS AS SHOWN IN THE STATEMENT(S) FILED 24 SEP 2013 . |
|
| DA3 | Amendments made section 104 |
Free format text: THE NATURE OF THE AMENDMENT IS AS SHOWN IN THE STATEMENT(S) FILED 24 SEP 2013 |
|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |