ES2376878T3 - Uso de brimonidina para prevenir y reducir la severidad de afecciones asociadas al estres - Google Patents
Uso de brimonidina para prevenir y reducir la severidad de afecciones asociadas al estres Download PDFInfo
- Publication number
- ES2376878T3 ES2376878T3 ES04755981T ES04755981T ES2376878T3 ES 2376878 T3 ES2376878 T3 ES 2376878T3 ES 04755981 T ES04755981 T ES 04755981T ES 04755981 T ES04755981 T ES 04755981T ES 2376878 T3 ES2376878 T3 ES 2376878T3
- Authority
- ES
- Spain
- Prior art keywords
- brimonidine
- mice
- clonidine
- deficient
- hypersensitivity
- 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.)
- Expired - Lifetime
Links
- XYLJNLCSTIOKRM-UHFFFAOYSA-N Alphagan Chemical compound C1=CC2=NC=CN=C2C(Br)=C1NC1=NCCN1 XYLJNLCSTIOKRM-UHFFFAOYSA-N 0.000 title claims abstract description 86
- 229960003679 brimonidine Drugs 0.000 title claims abstract description 74
- 230000009467 reduction Effects 0.000 claims abstract description 14
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- 150000001408 amides Chemical class 0.000 claims abstract description 6
- 206010020751 Hypersensitivity Diseases 0.000 claims description 77
- 208000026935 allergic disease Diseases 0.000 claims description 74
- 230000009610 hypersensitivity Effects 0.000 claims description 74
- 150000001875 compounds Chemical class 0.000 claims description 22
- 208000019695 Migraine disease Diseases 0.000 claims description 16
- 230000001953 sensory effect Effects 0.000 claims description 14
- 206010027599 migraine Diseases 0.000 claims description 13
- 239000012453 solvate Substances 0.000 claims description 5
- 238000007910 systemic administration Methods 0.000 claims description 4
- 150000001204 N-oxides Chemical class 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 13
- 239000000203 mixture Substances 0.000 abstract description 10
- 208000024891 symptom Diseases 0.000 abstract description 7
- 150000002148 esters Chemical class 0.000 abstract 1
- 230000002757 inflammatory effect Effects 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 88
- 230000002950 deficient Effects 0.000 description 59
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 51
- 229960002896 clonidine Drugs 0.000 description 51
- UQZVCDCIMBLVNR-TWYODKAFSA-N sulprostone Chemical compound O[C@@H]1CC(=O)[C@H](C\C=C/CCCC(=O)NS(=O)(=O)C)[C@H]1\C=C\[C@@H](O)COC1=CC=CC=C1 UQZVCDCIMBLVNR-TWYODKAFSA-N 0.000 description 40
- 229960003400 sulprostone Drugs 0.000 description 40
- 239000000556 agonist Substances 0.000 description 39
- 102000005962 receptors Human genes 0.000 description 37
- 108020003175 receptors Proteins 0.000 description 37
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 31
- 229960001802 phenylephrine Drugs 0.000 description 31
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 25
- 230000000694 effects Effects 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 20
- 206010039897 Sedation Diseases 0.000 description 18
- 230000004044 response Effects 0.000 description 18
- 230000036280 sedation Effects 0.000 description 18
- 230000002889 sympathetic effect Effects 0.000 description 17
- 206010070834 Sensitisation Diseases 0.000 description 16
- 230000008313 sensitization Effects 0.000 description 16
- XFYDIVBRZNQMJC-UHFFFAOYSA-N tizanidine Chemical compound ClC=1C=CC2=NSN=C2C=1NC1=NCCN1 XFYDIVBRZNQMJC-UHFFFAOYSA-N 0.000 description 16
- 229960000488 tizanidine Drugs 0.000 description 16
- 239000003981 vehicle Substances 0.000 description 16
- 230000001965 increasing effect Effects 0.000 description 15
- 239000008194 pharmaceutical composition Substances 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 230000000202 analgesic effect Effects 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- 231100000673 dose–response relationship Toxicity 0.000 description 13
- 235000002639 sodium chloride Nutrition 0.000 description 13
- 239000000048 adrenergic agonist Substances 0.000 description 12
- 230000035945 sensitivity Effects 0.000 description 12
- 108060003345 Adrenergic Receptor Proteins 0.000 description 11
- 102000017910 Adrenergic receptor Human genes 0.000 description 11
- 238000007912 intraperitoneal administration Methods 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 210000002820 sympathetic nervous system Anatomy 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 238000007913 intrathecal administration Methods 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 8
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 8
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- -1 dihydrochloride Chemical compound 0.000 description 7
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 229960002748 norepinephrine Drugs 0.000 description 7
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- 101150051188 Adora2a gene Proteins 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000000692 Student's t-test Methods 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000006698 induction Effects 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 229960004640 memantine Drugs 0.000 description 6
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 6
- 230000002093 peripheral effect Effects 0.000 description 6
- 229940044551 receptor antagonist Drugs 0.000 description 6
- 239000002464 receptor antagonist Substances 0.000 description 6
- 241000283690 Bos taurus Species 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 101150058615 Ptger1 gene Proteins 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- HRLIOXLXPOHXTA-NSHDSACASA-N dexmedetomidine Chemical compound C1([C@@H](C)C=2C(=C(C)C=CC=2)C)=CN=C[N]1 HRLIOXLXPOHXTA-NSHDSACASA-N 0.000 description 5
- 229960004253 dexmedetomidine Drugs 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- 230000003137 locomotive effect Effects 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 5
- 229960001289 prazosin Drugs 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000012353 t test Methods 0.000 description 5
- IRAOSCSPAYZRJE-UHFFFAOYSA-N 5-bromoquinoxalin-6-amine Chemical compound N1=CC=NC2=C(Br)C(N)=CC=C21 IRAOSCSPAYZRJE-UHFFFAOYSA-N 0.000 description 4
- 241000699800 Cricetinae Species 0.000 description 4
- SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 208000000060 Migraine with aura Diseases 0.000 description 4
- 102100035842 Prostaglandin E2 receptor EP1 subtype Human genes 0.000 description 4
- 230000005856 abnormality Effects 0.000 description 4
- OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000013265 extended release Methods 0.000 description 4
- 230000037023 motor activity Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 229950010131 puromycin Drugs 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 206010034960 Photophobia Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000001800 adrenalinergic effect Effects 0.000 description 3
- 230000036592 analgesia Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 230000001593 cAMP accumulation Effects 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000011260 co-administration Methods 0.000 description 3
- 238000002825 functional assay Methods 0.000 description 3
- 229960002870 gabapentin Drugs 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 238000011813 knockout mouse model Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 208000035824 paresthesia Diseases 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000003518 presynaptic effect Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000001177 retroviral effect Effects 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- YKGMGCYABGHZRB-UHFFFAOYSA-N 5-bromoquinoxalin-6-amine;hydrobromide Chemical compound Br.N1=CC=NC2=C(Br)C(N)=CC=C21 YKGMGCYABGHZRB-UHFFFAOYSA-N 0.000 description 2
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 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 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 206010019233 Headaches Diseases 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
- 229930195725 Mannitol Natural products 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 206010054956 Phonophobia Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229940003677 alphagan Drugs 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000002051 biphasic effect Effects 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 239000007933 dermal patch Substances 0.000 description 2
- 239000006196 drop Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000006742 locomotor activity Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 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
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 208000004296 neuralgia Diseases 0.000 description 2
- 208000021722 neuropathic pain Diseases 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 230000001242 postsynaptic effect Effects 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 2
- 239000000018 receptor agonist Substances 0.000 description 2
- 229940044601 receptor agonist Drugs 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000001624 sedative effect Effects 0.000 description 2
- 230000009155 sensory pathway Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-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
- VOQPQBGCWBEYEV-AWEZNQCLSA-N (S)-1-(4-bromoacetamidobenzyl)EDTA Chemical compound OC(=O)CN(CC(O)=O)C[C@@H](N(CC(O)=O)CC(O)=O)CC1=CC=C(NC(=O)CBr)C=C1 VOQPQBGCWBEYEV-AWEZNQCLSA-N 0.000 description 1
- JCIIKRHCWVHVFF-UHFFFAOYSA-N 1,2,4-thiadiazol-5-amine;hydrochloride Chemical compound Cl.NC1=NC=NS1 JCIIKRHCWVHVFF-UHFFFAOYSA-N 0.000 description 1
- IWEGDQUCWQFKHS-UHFFFAOYSA-N 1-(1,3-dioxolan-2-ylmethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN(CC2OCCO2)N=C1 IWEGDQUCWQFKHS-UHFFFAOYSA-N 0.000 description 1
- KIJKTBBMRJFEBK-UHFFFAOYSA-N 1-(2-aminoethyl)-1-(5-bromoquinoxalin-6-yl)thiourea Chemical compound N1=CC=NC2=C(Br)C(N(C(N)=S)CCN)=CC=C21 KIJKTBBMRJFEBK-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
- DGBBBEKLSZQFSV-UHFFFAOYSA-N 6-bromo-6-isothiocyanato-5h-quinoxaline Chemical compound C1=CN=C2C=CC(Br)(N=C=S)CC2=N1 DGBBBEKLSZQFSV-UHFFFAOYSA-N 0.000 description 1
- 206010049714 Abdominal migraine Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 1
- 206010050258 Basilar migraine Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 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
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- FEWJPZIEWOKRBE-LWMBPPNESA-L D-tartrate(2-) Chemical compound [O-]C(=O)[C@@H](O)[C@H](O)C([O-])=O FEWJPZIEWOKRBE-LWMBPPNESA-L 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000003164 Diplopia Diseases 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
- 101710091045 Envelope protein Proteins 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- OUVXYXNWSVIOSJ-UHFFFAOYSA-N Fluo-4 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(F)C(=O)C=C3OC3=CC(O)=C(F)C=C32)N(CC(O)=O)CC(O)=O)=C1 OUVXYXNWSVIOSJ-UHFFFAOYSA-N 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 208000004454 Hyperalgesia Diseases 0.000 description 1
- 206010020710 Hyperphagia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-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
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 206010062575 Muscle contracture Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- WXOMTJVVIMOXJL-BOBFKVMVSA-A O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)OS(=O)(=O)OC[C@H]1O[C@@H](O[C@]2(COS(=O)(=O)O[Al](O)O)O[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@@H]2OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@@H]1OS(=O)(=O)O[Al](O)O Chemical compound O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)OS(=O)(=O)OC[C@H]1O[C@@H](O[C@]2(COS(=O)(=O)O[Al](O)O)O[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@@H]2OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@@H]1OS(=O)(=O)O[Al](O)O WXOMTJVVIMOXJL-BOBFKVMVSA-A 0.000 description 1
- 208000005056 Ophthalmoplegic Migraine Diseases 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 101150053131 PTGER3 gene Proteins 0.000 description 1
- 206010033664 Panic attack Diseases 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 208000007542 Paresis Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 102100024447 Prostaglandin E2 receptor EP3 subtype Human genes 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 206010052784 Retinal migraine Diseases 0.000 description 1
- 206010039729 Scotoma Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 102100021696 Syncytin-1 Human genes 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000008548 Tension-Type Headache Diseases 0.000 description 1
- 208000012886 Vertigo Diseases 0.000 description 1
- 241000711975 Vesicular stomatitis virus Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- YHFXJKYHUWPWSJ-UHFFFAOYSA-L [Na+].[Na+].OS([O-])=O.OS([O-])=O Chemical class [Na+].[Na+].OS([O-])=O.OS([O-])=O YHFXJKYHUWPWSJ-UHFFFAOYSA-L 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229940126157 adrenergic receptor agonist Drugs 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 206010053552 allodynia Diseases 0.000 description 1
- WYTGDNHDOZPMIW-RCBQFDQVSA-N alstonine Natural products C1=CC2=C3C=CC=CC3=NC2=C2N1C[C@H]1[C@H](C)OC=C(C(=O)OC)[C@H]1C2 WYTGDNHDOZPMIW-RCBQFDQVSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 1
- 229960003805 amantadine Drugs 0.000 description 1
- WOLHOYHSEKDWQH-UHFFFAOYSA-N amantadine hydrochloride Chemical compound [Cl-].C1C(C2)CC3CC2CC1([NH3+])C3 WOLHOYHSEKDWQH-UHFFFAOYSA-N 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 201000007201 aphasia Diseases 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001908 autoinhibitory effect Effects 0.000 description 1
- OISFUZRUIGGTSD-LJTMIZJLSA-N azane;(2r,3r,4r,5s)-6-(methylamino)hexane-1,2,3,4,5-pentol Chemical compound N.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO OISFUZRUIGGTSD-LJTMIZJLSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 210000001841 basilar artery Anatomy 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000008901 benefit Effects 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
- 235000010233 benzoic acid Nutrition 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
- 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 1
- 238000009835 boiling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000011449 brick Substances 0.000 description 1
- 229960001724 brimonidine tartrate Drugs 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229940090805 clavulanate Drugs 0.000 description 1
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 208000006111 contracture Diseases 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 229940009662 edetate Drugs 0.000 description 1
- 229950008913 edisilate Drugs 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 229950005627 embonate Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 229950000206 estolate Drugs 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229940050411 fumarate Drugs 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- 108010027225 gag-pol Fusion Proteins Proteins 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 208000018685 gastrointestinal system disease Diseases 0.000 description 1
- 238000002695 general anesthesia Methods 0.000 description 1
- 229960001731 gluceptate Drugs 0.000 description 1
- KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 206010019465 hemiparesis Diseases 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 229960004716 idoxuridine Drugs 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 208000017420 migraine with brainstem aura Diseases 0.000 description 1
- 206010052787 migraine without aura Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 229950006327 napsilate Drugs 0.000 description 1
- 230000008035 nerve activity Effects 0.000 description 1
- 210000001640 nerve ending Anatomy 0.000 description 1
- 230000007383 nerve stimulation Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 235000020830 overeating Nutrition 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 210000001696 pelvic girdle Anatomy 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229940096826 phenylmercuric acetate Drugs 0.000 description 1
- PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 210000004044 posterior horn cell Anatomy 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 1
- 239000002522 prostaglandin receptor stimulating agent Substances 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000003236 psychic effect Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- MSGRFBKVMUKEGZ-UHFFFAOYSA-N quinoxalin-6-amine Chemical compound N1=CC=NC2=CC(N)=CC=C21 MSGRFBKVMUKEGZ-UHFFFAOYSA-N 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 238000003653 radioligand binding assay Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 239000004296 sodium metabisulphite Substances 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- ILJOYZVVZZFIKA-UHFFFAOYSA-M sodium;1,1-dioxo-1,2-benzothiazol-3-olate;hydrate Chemical compound O.[Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 ILJOYZVVZZFIKA-UHFFFAOYSA-M 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 210000002330 subarachnoid space Anatomy 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 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
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 238000001521 two-tailed test Methods 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 231100000889 vertigo Toxicity 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Nutrition Science (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Obesity (AREA)
- Rheumatology (AREA)
- Emergency Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hematology (AREA)
- Physical Education & Sports Medicine (AREA)
- Psychology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/607,439 US20040266776A1 (en) | 2003-06-25 | 2003-06-25 | Methods of preventing and reducing the severity of stress-associated conditions |
| US607439 | 2003-06-25 | ||
| PCT/US2004/020194 WO2005002580A1 (en) | 2003-06-25 | 2004-06-22 | Use of brimonidine for preventing and reducing the severity of stress-associated conditions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2376878T3 true ES2376878T3 (es) | 2012-03-20 |
Family
ID=33540268
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES04755981T Expired - Lifetime ES2376878T3 (es) | 2003-06-25 | 2004-06-22 | Uso de brimonidina para prevenir y reducir la severidad de afecciones asociadas al estres |
Country Status (14)
| Country | Link |
|---|---|
| US (6) | US20040266776A1 (enExample) |
| EP (1) | EP1638569B1 (enExample) |
| JP (2) | JP2007524625A (enExample) |
| KR (1) | KR20060023575A (enExample) |
| CN (2) | CN102579448A (enExample) |
| AT (1) | ATE539751T1 (enExample) |
| AU (2) | AU2004253500A1 (enExample) |
| BR (1) | BRPI0411826A (enExample) |
| CA (1) | CA2530487C (enExample) |
| DK (1) | DK1638569T3 (enExample) |
| ES (1) | ES2376878T3 (enExample) |
| MX (1) | MXPA05013900A (enExample) |
| TW (1) | TWI371276B (enExample) |
| WO (1) | WO2005002580A1 (enExample) |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5869079A (en) * | 1995-06-02 | 1999-02-09 | Oculex Pharmaceuticals, Inc. | Formulation for controlled release of drugs by combining hydrophilic and hydrophobic agents |
| US6726918B1 (en) | 2000-07-05 | 2004-04-27 | Oculex Pharmaceuticals, Inc. | Methods for treating inflammation-mediated conditions of the eye |
| WO2002043785A2 (en) | 2000-11-29 | 2002-06-06 | Oculex Pharmaceuticals, Inc. | Intraocular implants for preventing transplant rejection in the eye |
| US20050048099A1 (en) | 2003-01-09 | 2005-03-03 | Allergan, Inc. | Ocular implant made by a double extrusion process |
| US8410102B2 (en) | 2003-05-27 | 2013-04-02 | Galderma Laboratories Inc. | Methods and compositions for treating or preventing erythema |
| US7439241B2 (en) * | 2003-05-27 | 2008-10-21 | Galderma Laboratories, Inc. | Compounds, formulations, and methods for treating or preventing rosacea |
| US20050020600A1 (en) * | 2003-07-23 | 2005-01-27 | Scherer Warren J. | Methods of treating cutaneous flushing using selective alpha-2-adrenergic receptor agonists |
| US20050059744A1 (en) * | 2003-09-12 | 2005-03-17 | Allergan, Inc. | Methods and compositions for the treatment of pain and other alpha 2 adrenergic-mediated conditions |
| US7812049B2 (en) * | 2004-01-22 | 2010-10-12 | Vicept Therapeutics, Inc. | Method and therapeutic/cosmetic topical compositions for the treatment of rosacea and skin erythema using α1-adrenoceptor agonists |
| US20100266638A1 (en) | 2004-02-26 | 2010-10-21 | Allergan, Inc. | Headache treatment method |
| US20050244469A1 (en) | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Extended therapeutic effect ocular implant treatments |
| US20050244463A1 (en) | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Sustained release intraocular implants and methods for treating ocular vasculopathies |
| DK1761266T3 (da) * | 2004-05-25 | 2013-08-05 | Galderma Pharma Sa | Forbindelser, formuleringer og fremgangsmåder til at behandle eller forebygge inflammatoriske hudsygdomme |
| US8802128B2 (en) | 2006-06-23 | 2014-08-12 | Allergan, Inc. | Steroid-containing sustained release intraocular implants and related methods |
| WO2008144399A1 (en) * | 2007-05-18 | 2008-11-27 | Bausch & Lomb Incorporated | COMPLEXES COMPRISING α2-ADRENERGIC RECEPTOR AGONISTS AND COMPOSITIONS |
| PT2182960E (pt) * | 2007-07-27 | 2014-06-11 | Galderma Lab Inc | Compostos, formulações e métodos para a redução das rugas, da flacidez e dos sulcos na pele |
| US20090061020A1 (en) * | 2007-08-31 | 2009-03-05 | Theobald Klaus P | Brimonidine Compositions for Treating Erythema |
| US8455548B2 (en) | 2007-10-18 | 2013-06-04 | Allergan, Inc. | Method of treating sensorimotor disorders with alpha-2 adrenergic receptor agonists |
| US20110269805A1 (en) * | 2007-10-18 | 2011-11-03 | Gil Daniel W | Method of treating sensorimotor disorders with 4-(1-(2,3-dimethylphenyl)ethyl)-1h-imidazole-2(3h)-thione |
| US8470337B2 (en) * | 2008-03-13 | 2013-06-25 | Allergan, Inc. | Therapeutic treatments using botulinum neurotoxin |
| US12246013B2 (en) | 2008-08-01 | 2025-03-11 | Eye Therapies Llc | Vasoconstriction compositions and methods of use |
| DK2320911T3 (da) | 2008-08-01 | 2014-11-03 | Eye Therapies Llc | Vasokonstriktionspræparater og fremgangsmåder til anvendelse deraf |
| US8952011B2 (en) | 2008-08-01 | 2015-02-10 | Eye Therapies Llc | Compositions and methods for the treatment of nasal conditions |
| US20100203165A1 (en) * | 2008-08-01 | 2010-08-12 | Gerald Horn | Compositions and methods for treatment of disorders or conditions of the eye |
| US8987270B2 (en) | 2009-07-27 | 2015-03-24 | Eye Therapies Llc | Formulations of selective alpha-2 agonists and methods of use thereof |
| WO2011028621A1 (en) * | 2009-08-26 | 2011-03-10 | Allergan, Inc. | Method of treating compulsive disorders with alpha-2b adrenergic receptor agonists |
| NZ628266A (en) | 2009-11-09 | 2016-02-26 | Allergan Inc | Compositions and methods for stimulating hair growth |
| EP2329849B1 (en) | 2009-11-18 | 2015-04-29 | Galderma Research & Development | Combination of alpha-2 adrenergic receptor agonist and non-steroidal anti-inflammatory agent for treating or preventing an inflammatory skin disorder |
| US8394800B2 (en) * | 2009-11-19 | 2013-03-12 | Galderma Laboratories, L.P. | Method for treating psoriasis |
| WO2011075621A1 (en) * | 2009-12-17 | 2011-06-23 | Alpha Synergy Development, Inc. | Compositions and methods for ophthalmic delivery of nasal decongestants |
| JP5747392B2 (ja) | 2010-03-26 | 2015-07-15 | ガルデルマ・リサーチ・アンド・デヴェロップメント | 毛細血管拡張症の安全かつ有効な治療のための改善された方法および組成物 |
| AU2011231543B2 (en) | 2010-03-26 | 2015-01-15 | Galderma Research & Development | Improved methods and compositions for safe and effective treatment of erythema |
| US20120073515A1 (en) * | 2010-09-28 | 2012-03-29 | Advanced Bionics Corporation | Intrathecal needle guide apparatus |
| DK2444068T4 (en) | 2010-10-21 | 2018-03-05 | Galderma Sa | Brimonide sub-composition |
| US8053427B1 (en) | 2010-10-21 | 2011-11-08 | Galderma R&D SNC | Brimonidine gel composition |
| US8445526B2 (en) | 2011-02-03 | 2013-05-21 | Glaucoma & Nasal Therapies Llc | Compositions and methods for treatment of glaucoma |
| BR112014000634A2 (pt) | 2011-07-14 | 2017-02-14 | Allergan Inc | métodos para tratamento de incontinência associada com atividade sexual |
| AU2014216112B2 (en) | 2013-02-15 | 2019-02-21 | Allergan, Inc. | Sustained drug delivery implant |
| US8999938B2 (en) | 2013-06-21 | 2015-04-07 | Gnt Llc | Ophthalmic lipophilic drug delivery vehicle formulations |
| CA3006962A1 (en) * | 2014-12-01 | 2016-06-09 | Achelios Therapeutics Inc. | Methods and compositions for treating migraine and conditions associated with pain |
| MX2021001645A (es) * | 2018-08-29 | 2021-05-12 | Cellix Bio Private Ltd | Metodos y composiciones oftalmicas para el tratamiento de trastornos del ojo y enfermedades de la piel. |
| JP7534795B2 (ja) | 2019-05-01 | 2024-08-15 | クレキシオ バイオサイエンシーズ エルティーディー． | そう痒症を治療する方法 |
| CN120938924B (zh) * | 2025-10-17 | 2025-12-16 | 杭州云柏医药科技有限公司 | 一种盐酸乌拉地尔注射液及其制备方法 |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5380754A (en) * | 1988-02-29 | 1995-01-10 | Virotex Corporation | Topical composition enhancing healing of viral lesions |
| US6323204B1 (en) * | 1993-10-13 | 2001-11-27 | Allergan | Methods for using (2-imidazolin-2-ylamino) quinoxaline derivatives |
| CA2173974C (en) * | 1993-10-13 | 2006-05-02 | James A. Burke | Methods for using (2-imidazolin-2-ylamino) quinoxaline derivatives |
| US6462077B1 (en) * | 1993-12-28 | 2002-10-08 | Allergan, Inc. | Thromboxane ligands without blood clotting side effects |
| GB9425211D0 (en) * | 1994-12-14 | 1995-02-15 | Ucb Sa | Substituted 1H-imidazoles |
| WO1996025163A1 (en) | 1995-02-14 | 1996-08-22 | Board Of Supervisors Or Louisiana State Universityof Agricultural And Mechanical College Through Itsmedical Center | Treatment of herpes simplex viruses |
| US6194415B1 (en) * | 1995-06-28 | 2001-02-27 | Allergan Sales, Inc. | Method of using (2-imidazolin-2-ylamino) quinoxoalines in treating neural injury |
| US5795909A (en) | 1996-05-22 | 1998-08-18 | Neuromedica, Inc. | DHA-pharmaceutical agent conjugates of taxanes |
| US6576636B2 (en) | 1996-05-22 | 2003-06-10 | Protarga, Inc. | Method of treating a liver disorder with fatty acid-antiviral agent conjugates |
| AU1827799A (en) | 1997-12-15 | 1999-07-05 | Axia Therapeutics, Inc. | Oral delivery formulation |
| US20030059471A1 (en) | 1997-12-15 | 2003-03-27 | Compton Bruce Jon | Oral delivery formulation |
| CA2340225A1 (en) | 1998-10-27 | 2000-05-04 | Wesley Wehsin Han | Preservative system for topically administrable pharmaceutical compositions containing a fatty acid/amino acid soap |
| AU768393B2 (en) * | 1999-05-28 | 2003-12-11 | Jeffrey Berlant | Compounds and methods for the treatment of post traumatic stress disorder |
| AU5331200A (en) | 1999-06-11 | 2001-01-02 | Ohio State University Research Foundation, The | Methods and compositions for treating raynaud's phenomenon and scleroderma |
| KR100331529B1 (ko) | 1999-06-16 | 2002-04-06 | 민경윤 | 난용성 항진균제의 경구투여용 조성물 및 그의 제조 방법 |
| US7160890B2 (en) | 1999-12-02 | 2007-01-09 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A3 receptor and uses thereof |
| IN188750B (enExample) | 1999-12-04 | 2002-11-02 | Khamar Bakulesh Dr Mafatlal | |
| US6294553B1 (en) * | 2000-02-15 | 2001-09-25 | Allergan Sales, Inc. | Method for treating ocular pain |
| US6444681B1 (en) | 2000-06-09 | 2002-09-03 | The Ohio State University Research Foundation | Methods and compositions for treating Raynaud's Phenomenon and scleroderma |
| WO2002005853A2 (en) * | 2000-07-14 | 2002-01-24 | Allergan, Inc. | Compositions containing alpha-2-adrenergic agonist components |
| US6673802B2 (en) | 2000-12-01 | 2004-01-06 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A3 receptor and uses thereof |
| JP2005529062A (ja) | 2001-11-30 | 2005-09-29 | オーエスアイ・ファーマスーティカルズ・インコーポレーテッド | アデノシンａ１及びａ３受容体に特異的な化合物とその使用 |
| IL147921A0 (en) * | 2002-01-31 | 2002-08-14 | Abdulrazik Mohammad | A method for treating central nervous system disorders by ocular dosing |
| US7345065B2 (en) * | 2002-05-21 | 2008-03-18 | Allergan, Inc. | Methods and compositions for alleviating pain |
| US7439241B2 (en) | 2003-05-27 | 2008-10-21 | Galderma Laboratories, Inc. | Compounds, formulations, and methods for treating or preventing rosacea |
| US20050020600A1 (en) | 2003-07-23 | 2005-01-27 | Scherer Warren J. | Methods of treating cutaneous flushing using selective alpha-2-adrenergic receptor agonists |
| DK1761266T3 (da) | 2004-05-25 | 2013-08-05 | Galderma Pharma Sa | Forbindelser, formuleringer og fremgangsmåder til at behandle eller forebygge inflammatoriske hudsygdomme |
-
2003
- 2003-06-25 US US10/607,439 patent/US20040266776A1/en not_active Abandoned
-
2004
- 2004-06-22 CA CA2530487A patent/CA2530487C/en not_active Expired - Fee Related
- 2004-06-22 AU AU2004253500A patent/AU2004253500A1/en not_active Abandoned
- 2004-06-22 JP JP2006517594A patent/JP2007524625A/ja active Pending
- 2004-06-22 MX MXPA05013900A patent/MXPA05013900A/es active IP Right Grant
- 2004-06-22 CN CN2011104449533A patent/CN102579448A/zh active Pending
- 2004-06-22 WO PCT/US2004/020194 patent/WO2005002580A1/en not_active Ceased
- 2004-06-22 ES ES04755981T patent/ES2376878T3/es not_active Expired - Lifetime
- 2004-06-22 KR KR1020057024881A patent/KR20060023575A/ko not_active Withdrawn
- 2004-06-22 AT AT04755981T patent/ATE539751T1/de active
- 2004-06-22 BR BRPI0411826-0A patent/BRPI0411826A/pt not_active IP Right Cessation
- 2004-06-22 CN CNA2004800178422A patent/CN1812791A/zh active Pending
- 2004-06-22 EP EP04755981A patent/EP1638569B1/en not_active Expired - Lifetime
- 2004-06-22 DK DK04755981.0T patent/DK1638569T3/da active
- 2004-06-25 TW TW093118660A patent/TWI371276B/zh not_active IP Right Cessation
-
2008
- 2008-05-02 US US12/114,727 patent/US7977335B2/en not_active Expired - Lifetime
- 2008-05-02 US US12/114,719 patent/US20080207627A1/en not_active Abandoned
-
2010
- 2010-11-18 AU AU2010241513A patent/AU2010241513B9/en not_active Ceased
-
2011
- 2011-12-13 JP JP2011272494A patent/JP2012092123A/ja active Pending
-
2012
- 2012-06-01 US US13/486,847 patent/US20120302574A1/en not_active Abandoned
- 2012-10-15 US US13/652,179 patent/US20130102612A1/en not_active Abandoned
-
2013
- 2013-02-15 US US13/768,901 patent/US20130217694A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US7977335B2 (en) | 2011-07-12 |
| MXPA05013900A (es) | 2006-02-24 |
| HK1090282A1 (en) | 2006-12-22 |
| AU2004253500A1 (en) | 2005-01-13 |
| CN1812791A (zh) | 2006-08-02 |
| ATE539751T1 (de) | 2012-01-15 |
| US20130217694A1 (en) | 2013-08-22 |
| EP1638569B1 (en) | 2012-01-04 |
| DK1638569T3 (da) | 2012-04-02 |
| AU2010241513B9 (en) | 2011-10-20 |
| US20120302574A1 (en) | 2012-11-29 |
| TWI371276B (en) | 2012-09-01 |
| US20040266776A1 (en) | 2004-12-30 |
| AU2010241513A1 (en) | 2010-12-09 |
| WO2005002580A1 (en) | 2005-01-13 |
| US20080207627A1 (en) | 2008-08-28 |
| JP2012092123A (ja) | 2012-05-17 |
| CA2530487A1 (en) | 2005-01-13 |
| US20130102612A1 (en) | 2013-04-25 |
| TW200524611A (en) | 2005-08-01 |
| BRPI0411826A (pt) | 2006-08-08 |
| KR20060023575A (ko) | 2006-03-14 |
| EP1638569A1 (en) | 2006-03-29 |
| AU2010241513B2 (en) | 2011-09-22 |
| US20080207628A1 (en) | 2008-08-28 |
| CN102579448A (zh) | 2012-07-18 |
| CA2530487C (en) | 2011-11-01 |
| JP2007524625A (ja) | 2007-08-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2376878T3 (es) | Uso de brimonidina para prevenir y reducir la severidad de afecciones asociadas al estres | |
| TWI353835B (en) | Novel methods for identifying improved, non-sedati | |
| CA2486716C (en) | Compositions and their uses for alleviating pain | |
| Pertovaara et al. | Pharmacological properties, central nervous system effects, and potential therapeutic applications of atipamezole, a selective α2‐adrenoceptor antagonist | |
| BR112020024261A2 (pt) | composto da fórmula (i), composições farmacêuticas e método de prevenção | |
| HK1090282B (en) | Use of brimonidine for preventing and reducing the severity of stress-associated conditions | |
| JP4362457B2 (ja) | 神経因性疼痛治療剤 | |
| HK1173372A (en) | Use of brimonidine for preventing and reducing the severity of stress-associated conditions |