JP2004505930A - 心房細動の予防または治療のための薬物の製造における５ｈｔ４受容体アンタゴニストの使用 - Google Patents
心房細動の予防または治療のための薬物の製造における５ｈｔ４受容体アンタゴニストの使用 Download PDFInfo
- Publication number
- JP2004505930A JP2004505930A JP2002517100A JP2002517100A JP2004505930A JP 2004505930 A JP2004505930 A JP 2004505930A JP 2002517100 A JP2002517100 A JP 2002517100A JP 2002517100 A JP2002517100 A JP 2002517100A JP 2004505930 A JP2004505930 A JP 2004505930A
- Authority
- JP
- Japan
- Prior art keywords
- atrial
- mammal
- antagonist
- treatment
- salt
- 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.)
- Pending
Links
- 206010003658 Atrial Fibrillation Diseases 0.000 title claims abstract description 192
- 238000011282 treatment Methods 0.000 title claims abstract description 78
- 230000002265 prevention Effects 0.000 title claims abstract description 60
- 239000003814 drug Substances 0.000 title claims abstract description 41
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 25
- 239000003523 serotonin 4 antagonist Substances 0.000 title claims description 20
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims abstract description 206
- KVCSJPATKXABRQ-UHFFFAOYSA-N piboserod Chemical compound C1CN(CCCC)CCC1CNC(=O)C(C1=CC=CC=C11)=C2N1CCCO2 KVCSJPATKXABRQ-UHFFFAOYSA-N 0.000 claims abstract description 195
- 150000003839 salts Chemical class 0.000 claims abstract description 112
- 238000000034 method Methods 0.000 claims abstract description 96
- 241000124008 Mammalia Species 0.000 claims abstract description 92
- 208000032845 Atrial Remodeling Diseases 0.000 claims abstract description 66
- 239000005557 antagonist Substances 0.000 claims abstract description 58
- -1 butyl-4-piperidinyl Chemical group 0.000 claims abstract description 55
- 238000012423 maintenance Methods 0.000 claims abstract description 39
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 27
- 206010003130 Arrhythmia supraventricular Diseases 0.000 claims abstract description 21
- 238000011321 prophylaxis Methods 0.000 claims abstract 6
- 230000001746 atrial effect Effects 0.000 claims description 111
- 239000002464 receptor antagonist Substances 0.000 claims description 65
- 229940044551 receptor antagonist Drugs 0.000 claims description 54
- 150000001875 compounds Chemical class 0.000 claims description 45
- 239000012458 free base Substances 0.000 claims description 31
- 230000000694 effects Effects 0.000 claims description 29
- 238000013194 cardioversion Methods 0.000 claims description 25
- 230000033764 rhythmic process Effects 0.000 claims description 21
- 230000002085 persistent effect Effects 0.000 claims description 20
- 230000037396 body weight Effects 0.000 claims description 19
- 230000037024 effective refractory period Effects 0.000 claims description 18
- 230000001965 increasing effect Effects 0.000 claims description 18
- 238000012986 modification Methods 0.000 claims description 18
- 230000004048 modification Effects 0.000 claims description 18
- 201000010099 disease Diseases 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 229940079593 drug Drugs 0.000 claims description 17
- 241000282412 Homo Species 0.000 claims description 16
- 230000001314 paroxysmal effect Effects 0.000 claims description 15
- 210000002837 heart atrium Anatomy 0.000 claims description 13
- QEZYDSSGVBTNBH-UHFFFAOYSA-N n-[2-[4-(adamantane-1-carbonylamino)piperidin-1-yl]ethyl]-1-propan-2-ylindazole-3-carboxamide Chemical compound C12=CC=CC=C2N(C(C)C)N=C1C(=O)NCCN1CCC(NC(=O)C23CC4CC(CC(C4)C2)C3)CC1 QEZYDSSGVBTNBH-UHFFFAOYSA-N 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 230000005764 inhibitory process Effects 0.000 claims description 7
- MOZPSIXKYJUTKI-UHFFFAOYSA-N GR 113808 Chemical compound C12=CC=CC=C2N(C)C=C1C(=O)OCC1CCN(CCNS(C)(=O)=O)CC1 MOZPSIXKYJUTKI-UHFFFAOYSA-N 0.000 claims description 6
- 230000002763 arrhythmic effect Effects 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 230000009286 beneficial effect Effects 0.000 claims description 4
- 206010061592 cardiac fibrillation Diseases 0.000 claims description 4
- 230000003247 decreasing effect Effects 0.000 claims description 4
- 230000001419 dependent effect Effects 0.000 claims description 4
- 230000002600 fibrillogenic effect Effects 0.000 claims description 4
- VQJFDBXITIOGJM-UHFFFAOYSA-N hydron;[1-[2-(methanesulfonamido)ethyl]piperidin-4-yl]methyl 5-fluoro-2-methoxy-1h-indole-3-carboxylate;sulfamate Chemical compound NS(O)(=O)=O.COC=1NC2=CC=C(F)C=C2C=1C(=O)OCC1CCN(CCNS(C)(=O)=O)CC1 VQJFDBXITIOGJM-UHFFFAOYSA-N 0.000 claims description 3
- 238000004904 shortening Methods 0.000 claims description 3
- NBUGBCTWXCXBQD-UHFFFAOYSA-N n-[2-[4-[3-(5-amino-6-chloro-2,3-dihydro-1,4-benzodioxin-8-yl)-3-oxopropyl]piperidin-1-yl]ethyl]methanesulfonamide Chemical compound C1CN(CCNS(=O)(=O)C)CCC1CCC(=O)C1=CC(Cl)=C(N)C2=C1OCCO2 NBUGBCTWXCXBQD-UHFFFAOYSA-N 0.000 claims description 2
- ZMEZACDEDHDTCJ-UHFFFAOYSA-N 2h-[1,3]oxazino[3,2-a]indole-10-carboxamide Chemical compound C12=CC=CC=C2C(C(=O)N)=C2N1C=CCO2 ZMEZACDEDHDTCJ-UHFFFAOYSA-N 0.000 claims 1
- PQJNVHWSTANYGF-UHFFFAOYSA-N 5-amino-n-(1-butylpiperidin-4-yl)-6-chloro-3-methyl-2,3-dihydro-1,4-benzodioxine-8-carboxamide Chemical compound C1CN(CCCC)CCC1NC(=O)C1=CC(Cl)=C(N)C2=C1OCC(C)O2 PQJNVHWSTANYGF-UHFFFAOYSA-N 0.000 claims 1
- 230000002354 daily effect Effects 0.000 description 57
- 102000005962 receptors Human genes 0.000 description 39
- 108020003175 receptors Proteins 0.000 description 39
- 239000000203 mixture Substances 0.000 description 24
- 230000004044 response Effects 0.000 description 23
- 238000002474 experimental method Methods 0.000 description 22
- 239000003826 tablet Substances 0.000 description 20
- 238000012360 testing method Methods 0.000 description 16
- 238000001990 intravenous administration Methods 0.000 description 15
- 239000003981 vehicle Substances 0.000 description 14
- 244000309715 mini pig Species 0.000 description 13
- 230000036470 plasma concentration Effects 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- 230000008485 antagonism Effects 0.000 description 11
- 229910052739 hydrogen Inorganic materials 0.000 description 11
- 239000001257 hydrogen Substances 0.000 description 11
- 230000036279 refractory period Effects 0.000 description 11
- 230000008602 contraction Effects 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- 230000000638 stimulation Effects 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 230000001684 chronic effect Effects 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 230000000699 topical effect Effects 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- 239000003146 anticoagulant agent Substances 0.000 description 6
- 229940127219 anticoagulant drug Drugs 0.000 description 6
- 238000011161 development Methods 0.000 description 6
- 230000018109 developmental process Effects 0.000 description 6
- 231100000673 dose–response relationship Toxicity 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 6
- 238000007634 remodeling Methods 0.000 description 6
- 238000012552 review Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 229960005080 warfarin Drugs 0.000 description 6
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 6
- MKGIQRNAGSSHRV-UHFFFAOYSA-N 1,1-dimethyl-4-phenylpiperazin-1-ium Chemical compound C1C[N+](C)(C)CCN1C1=CC=CC=C1 MKGIQRNAGSSHRV-UHFFFAOYSA-N 0.000 description 5
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 5
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 230000002496 gastric effect Effects 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 238000005469 granulation Methods 0.000 description 5
- 230000003179 granulation Effects 0.000 description 5
- 125000001475 halogen functional group Chemical group 0.000 description 5
- 150000003840 hydrochlorides Chemical class 0.000 description 5
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 5
- 230000006698 induction Effects 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 4
- 241000282887 Suidae Species 0.000 description 4
- 125000003710 aryl alkyl group Chemical group 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- RBLGLDWTCZMLRW-UHFFFAOYSA-K dicalcium;phosphate;dihydrate Chemical compound O.O.[Ca+2].[Ca+2].[O-]P([O-])([O-])=O RBLGLDWTCZMLRW-UHFFFAOYSA-K 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 230000002526 effect on cardiovascular system Effects 0.000 description 4
- 210000001320 hippocampus Anatomy 0.000 description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 4
- 239000008108 microcrystalline cellulose Substances 0.000 description 4
- 229940016286 microcrystalline cellulose Drugs 0.000 description 4
- 238000012544 monitoring process Methods 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 229940079832 sodium starch glycolate Drugs 0.000 description 4
- 239000008109 sodium starch glycolate Substances 0.000 description 4
- 229920003109 sodium starch glycolate Polymers 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000700199 Cavia porcellus Species 0.000 description 3
- 206010033557 Palpitations Diseases 0.000 description 3
- 238000000540 analysis of variance Methods 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000002249 anxiolytic agent Substances 0.000 description 3
- 230000000949 anxiolytic effect Effects 0.000 description 3
- 230000003416 augmentation Effects 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- XAAHAAMILDNBPS-UHFFFAOYSA-L calcium hydrogenphosphate dihydrate Chemical compound O.O.[Ca+2].OP([O-])([O-])=O XAAHAAMILDNBPS-UHFFFAOYSA-L 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
- 210000001072 colon Anatomy 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 229920001903 high density polyethylene Polymers 0.000 description 3
- 239000004700 high-density polyethylene Substances 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 210000005248 left atrial appendage Anatomy 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000002287 radioligand Substances 0.000 description 3
- 230000003997 social interaction Effects 0.000 description 3
- 238000013175 transesophageal echocardiography Methods 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- MZRKHUUDDHJVHS-MOKVOYLWSA-N 3-ethyl-n-[(5s)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl]-2-oxobenzimidazole-1-carboxamide Chemical compound C1C(N2C)CC[C@H]2CC1NC(=O)N1C2=CC=CC=C2N(CC)C1=O MZRKHUUDDHJVHS-MOKVOYLWSA-N 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- 208000025962 Crush injury Diseases 0.000 description 2
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 102000014630 G protein-coupled serotonin receptor activity proteins Human genes 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 239000008896 Opium Substances 0.000 description 2
- 229920005439 Perspex® Polymers 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- 241000282898 Sus scrofa Species 0.000 description 2
- 208000001871 Tachycardia Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 230000003044 adaptive effect Effects 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 230000003444 anaesthetic effect Effects 0.000 description 2
- 239000003416 antiarrhythmic agent Substances 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- 230000006793 arrhythmia Effects 0.000 description 2
- 230000004872 arterial blood pressure Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229940049706 benzodiazepine Drugs 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 2
- 229960004484 carbachol Drugs 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229960004782 chlordiazepoxide Drugs 0.000 description 2
- ANTSCNMPPGJYLG-UHFFFAOYSA-N chlordiazepoxide Chemical compound O=N=1CC(NC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 ANTSCNMPPGJYLG-UHFFFAOYSA-N 0.000 description 2
- 230000001713 cholinergic effect Effects 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
- 239000010432 diamond Substances 0.000 description 2
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 2
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 2
- 229940038472 dicalcium phosphate Drugs 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 210000003238 esophagus Anatomy 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- MFWNKCLOYSRHCJ-BTTYYORXSA-N granisetron Chemical compound C1=CC=C2C(C(=O)N[C@H]3C[C@H]4CCC[C@@H](C3)N4C)=NN(C)C2=C1 MFWNKCLOYSRHCJ-BTTYYORXSA-N 0.000 description 2
- 229960003727 granisetron Drugs 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 230000001788 irregular Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 230000004899 motility Effects 0.000 description 2
- 229960002715 nicotine Drugs 0.000 description 2
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 2
- 229960001027 opium Drugs 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000004926 polymethyl methacrylate Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000008313 sensitization Effects 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000006794 tachycardia Effects 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000009423 ventilation Methods 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- HVRCLXXJIQTXHC-UHFFFAOYSA-N 1-methylindole-3-carboxylic acid Chemical compound C1=CC=C2N(C)C=C(C(O)=O)C2=C1 HVRCLXXJIQTXHC-UHFFFAOYSA-N 0.000 description 1
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- GZSKEXSLDPEFPT-HZMBPMFUSA-N 4-amino-n-[(4s,5s)-1-azabicyclo[3.3.1]nonan-4-yl]-5-chloro-2-methoxybenzamide Chemical compound COC1=CC(N)=C(Cl)C=C1C(=O)N[C@@H]1[C@H](C2)CCCN2CC1 GZSKEXSLDPEFPT-HZMBPMFUSA-N 0.000 description 1
- GHHFSINZUDUODS-UHFFFAOYSA-N 6-chloro-2,3-dihydro-1,4-benzodioxin-5-amine Chemical compound O1CCOC2=C1C=CC(Cl)=C2N GHHFSINZUDUODS-UHFFFAOYSA-N 0.000 description 1
- 102100024381 AF4/FMR2 family member 4 Human genes 0.000 description 1
- 229920001817 Agar Polymers 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
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010003662 Atrial flutter Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 108010009685 Cholinergic Receptors Proteins 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
- 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
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 101000833170 Homo sapiens AF4/FMR2 family member 4 Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010048858 Ischaemic cardiomyopathy Diseases 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 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
- 206010049694 Left Ventricular Dysfunction Diseases 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- RLJFTICUTYVZDG-UHFFFAOYSA-N Methiothepine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2CC1N1CCN(C)CC1 RLJFTICUTYVZDG-UHFFFAOYSA-N 0.000 description 1
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 1
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 1
- DPWPWRLQFGFJFI-UHFFFAOYSA-N Pargyline Chemical compound C#CCN(C)CC1=CC=CC=C1 DPWPWRLQFGFJFI-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 238000003639 Student–Newman–Keuls (SNK) method Methods 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
- 229930006000 Sucrose Natural products 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
- 241000364021 Tulsa Species 0.000 description 1
- IANSWOBHSSJGEG-UHFFFAOYSA-N [2-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl] carbamate Chemical compound C(N)(OC1=C(C=CC=C1)C1=NC(=NO1)C)=O IANSWOBHSSJGEG-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 102000034337 acetylcholine receptors Human genes 0.000 description 1
- 230000036982 action potential Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 230000003440 anti-fibrillation Effects 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 206010003668 atrial tachycardia Diseases 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000036471 bradycardia Effects 0.000 description 1
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- GTCAXTIRRLKXRU-UHFFFAOYSA-N carbamic acid methyl ester Natural products COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 230000009989 contractile response Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000032459 dedifferentiation Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000003205 diastolic effect Effects 0.000 description 1
- 229940084926 diazepam 2 mg Drugs 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- VONWDASPFIQPDY-UHFFFAOYSA-N dimethyl methylphosphonate Chemical compound COP(C)(=O)OC VONWDASPFIQPDY-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 210000004921 distal colon Anatomy 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 238000013195 electrical cardioversion Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000003073 embolic effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 230000003370 grooming effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229940125947 insurmountable antagonist Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- BWHLPLXXIDYSNW-UHFFFAOYSA-N ketorolac tromethamine Chemical compound OCC(N)(CO)CO.OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 BWHLPLXXIDYSNW-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000005246 left atrium Anatomy 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000011418 maintenance treatment Methods 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000002644 neurohormonal effect Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229960001779 pargyline Drugs 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229960002275 pentobarbital sodium Drugs 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 238000013310 pig model Methods 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000004886 process control Methods 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000002325 prokinetic agent Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000000541 pulsatile effect Effects 0.000 description 1
- 230000035485 pulse pressure Effects 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 230000036454 renin-angiotensin system Effects 0.000 description 1
- 210000005247 right atrial appendage Anatomy 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 210000002820 sympathetic nervous system Anatomy 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 230000007838 tissue remodeling Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 230000001515 vagal effect Effects 0.000 description 1
- 239000006200 vaporizer Substances 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Images
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
- A61K31/435—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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with heterocyclic ring systems
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1611—Inorganic compounds
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61P9/06—Antiarrhythmics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0019410A GB0019410D0 (en) | 2000-08-07 | 2000-08-07 | Novel use |
| GB0019523A GB0019523D0 (en) | 2000-08-08 | 2000-08-08 | Novel use |
| GB0019524A GB0019524D0 (en) | 2000-08-08 | 2000-08-08 | Novel use |
| GB0118919A GB0118919D0 (en) | 2001-08-02 | 2001-08-02 | Novel use |
| GB0119022A GB0119022D0 (en) | 2001-08-03 | 2001-08-03 | Novel use |
| PCT/GB2001/003544 WO2002011766A2 (en) | 2000-08-07 | 2001-08-07 | Use of 5ht4 receptor antagonists in the manufacture of a medicament for the prophylaxis or treatment of atrial fibrillation |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007062210A Division JP2007145869A (ja) | 2000-08-07 | 2007-03-12 | 心房細動の予防または治療のための薬物の製造における５ｈｔ４受容体アンタゴニストの使用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2004505930A true JP2004505930A (ja) | 2004-02-26 |
| JP2004505930A5 JP2004505930A5 (enExample) | 2005-04-21 |
Family
ID=27515972
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002517100A Pending JP2004505930A (ja) | 2000-08-07 | 2001-08-07 | 心房細動の予防または治療のための薬物の製造における５ｈｔ４受容体アンタゴニストの使用 |
| JP2007062210A Pending JP2007145869A (ja) | 2000-08-07 | 2007-03-12 | 心房細動の予防または治療のための薬物の製造における５ｈｔ４受容体アンタゴニストの使用 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007062210A Pending JP2007145869A (ja) | 2000-08-07 | 2007-03-12 | 心房細動の予防または治療のための薬物の製造における５ｈｔ４受容体アンタゴニストの使用 |
Country Status (16)
| Country | Link |
|---|---|
| US (3) | US20050032866A1 (enExample) |
| EP (1) | EP1311295A2 (enExample) |
| JP (2) | JP2004505930A (enExample) |
| KR (1) | KR20030027010A (enExample) |
| CN (1) | CN100413539C (enExample) |
| AU (1) | AU781276B2 (enExample) |
| BR (1) | BR0113073A (enExample) |
| CA (1) | CA2418904A1 (enExample) |
| CZ (1) | CZ2003366A3 (enExample) |
| HU (1) | HUP0303075A3 (enExample) |
| IL (1) | IL154279A0 (enExample) |
| MX (1) | MXPA03001210A (enExample) |
| NO (1) | NO20030588L (enExample) |
| NZ (1) | NZ524108A (enExample) |
| PL (1) | PL365048A1 (enExample) |
| WO (1) | WO2002011766A2 (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MXPA04007857A (es) * | 2002-02-14 | 2004-10-15 | Glaxo Group Ltd | Composicion farmaceutica que comprende n-((1-butil -4-piperidinil) metil)-3, 4-dihidro-2h -(1, 3)oxazino (3, 2-a)indol -10-carboxamida o sal de la misma, y procedimiento para la misma que comprende granulacion en seco. |
| GB0211230D0 (en) * | 2002-05-16 | 2002-06-26 | Medinnova Sf | Treatment of heart failure |
| EP2366431A1 (en) * | 2010-03-19 | 2011-09-21 | Universitätsklinikum Hamburg-Eppendorf | Myeloperoxidase as a target in atrial fibrillation |
| EP3176164B1 (en) | 2014-07-30 | 2019-08-21 | Aetas Pharma Co. Ltd. | Optical isomer of 1,4-benzothiazepine-1-oxide derivative, and pharmaceutical composition prepared using same |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9009389D0 (en) * | 1990-04-26 | 1990-06-20 | Smith Kline French Lab | Treatment |
| GB9103862D0 (en) * | 1991-02-25 | 1991-04-10 | Glaxo Group Ltd | Chemical compounds |
| CA2118812C (en) * | 1991-09-12 | 2006-01-17 | Francis David King | 5-ht4 receptor antagonists |
| MA22647A1 (fr) * | 1991-09-14 | 1993-04-01 | Smithkline Beecham Plc | Procede de preparation d'un ester ou d'un amide d'un nouveau produit . |
| US5998409A (en) * | 1992-03-12 | 1999-12-07 | Smithkline Beecham Plc | Condensed indole derivatives as 5HT4 -receptor antagonists |
| DE69325167T2 (de) * | 1992-03-12 | 2000-01-20 | Smithkline Beecham P.L.C., Brentford | Kondensierte indol-derivate als 5-ht4-rezeptor-antagonisten |
| US5852014A (en) * | 1992-03-12 | 1998-12-22 | Smithkline Beecham P.L.C. | Condensed indole derivatives as 5HT4 -receptor antagonists |
| GB9206989D0 (en) * | 1992-03-31 | 1992-05-13 | Glaxo Group Ltd | Chemical compounds |
| MX9301837A (es) * | 1992-03-31 | 1994-02-28 | Glaxo Group Ltd | Ureas y fenilcarbamatos substituidos, proceso para su preparacion y composicion farmaceutica que los comprende. |
| SK116394A3 (en) * | 1992-03-31 | 1995-04-12 | Glaxo Group Ltd | Substituted phenylcarbamates and ureas |
| ATE171446T1 (de) * | 1993-05-26 | 1998-10-15 | Syntex Inc | 1-phenylalkanone als 5-ht4 rezeptor ligande |
| IL117438A (en) * | 1995-03-16 | 2001-12-23 | Lilly Co Eli | Indazolecarboxamides, their preparation and pharmaceutical compositions containing them |
| ES2151743T3 (es) * | 1996-08-16 | 2001-01-01 | Smithkline Beecham Plc | Procedimiento para la preparacion de n-((1-n-butil-4-piperidinil)metil)-3,4-dihidro-2h-(1,3)-oxazino(3,2-a)indol-10-carboxamida y las sales y productos intermedios en el procedimiento. |
| NZ535261A (en) * | 2000-08-08 | 2004-12-24 | Smithkline Beecham P | A tablet comprising the hydrochloride salt of N-(1-nbutyl-4-piperidinyl)methyl]-3,4-[1,3]oxazino[3,2-a] indole-10-carboxamide |
-
2001
- 2001-08-07 MX MXPA03001210A patent/MXPA03001210A/es unknown
- 2001-08-07 CZ CZ2003366A patent/CZ2003366A3/cs unknown
- 2001-08-07 AU AU76529/01A patent/AU781276B2/en not_active Ceased
- 2001-08-07 US US10/344,075 patent/US20050032866A1/en not_active Abandoned
- 2001-08-07 CA CA002418904A patent/CA2418904A1/en not_active Abandoned
- 2001-08-07 BR BR0113073-0A patent/BR0113073A/pt not_active IP Right Cessation
- 2001-08-07 JP JP2002517100A patent/JP2004505930A/ja active Pending
- 2001-08-07 NZ NZ524108A patent/NZ524108A/en unknown
- 2001-08-07 CN CNB018169511A patent/CN100413539C/zh not_active Expired - Fee Related
- 2001-08-07 IL IL15427901A patent/IL154279A0/xx unknown
- 2001-08-07 KR KR10-2003-7001797A patent/KR20030027010A/ko not_active Ceased
- 2001-08-07 PL PL01365048A patent/PL365048A1/xx unknown
- 2001-08-07 EP EP01954184A patent/EP1311295A2/en not_active Withdrawn
- 2001-08-07 HU HU0303075A patent/HUP0303075A3/hu unknown
- 2001-08-07 WO PCT/GB2001/003544 patent/WO2002011766A2/en not_active Ceased
-
2003
- 2003-02-06 NO NO20030588A patent/NO20030588L/no not_active Application Discontinuation
-
2006
- 2006-09-20 US US11/533,542 patent/US20070015769A1/en not_active Abandoned
-
2007
- 2007-03-12 JP JP2007062210A patent/JP2007145869A/ja active Pending
- 2007-10-31 US US11/930,277 patent/US20080125422A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CN100413539C (zh) | 2008-08-27 |
| BR0113073A (pt) | 2004-06-22 |
| HUP0303075A3 (en) | 2007-03-28 |
| EP1311295A2 (en) | 2003-05-21 |
| MXPA03001210A (es) | 2004-08-12 |
| PL365048A1 (en) | 2004-12-27 |
| US20050032866A1 (en) | 2005-02-10 |
| WO2002011766A2 (en) | 2002-02-14 |
| WO2002011766A3 (en) | 2002-08-01 |
| IL154279A0 (en) | 2003-09-17 |
| NO20030588D0 (no) | 2003-02-06 |
| NO20030588L (no) | 2003-04-03 |
| US20070015769A1 (en) | 2007-01-18 |
| CZ2003366A3 (en) | 2004-04-14 |
| US20080125422A1 (en) | 2008-05-29 |
| CN1468112A (zh) | 2004-01-14 |
| AU781276B2 (en) | 2005-05-12 |
| AU7652901A (en) | 2002-02-18 |
| HUP0303075A2 (hu) | 2003-12-29 |
| NZ524108A (en) | 2004-11-26 |
| CA2418904A1 (en) | 2002-02-14 |
| KR20030027010A (ko) | 2003-04-03 |
| JP2007145869A (ja) | 2007-06-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5344620B2 (ja) | オルメサルタンメドキソミル及びアムロジピンの固形製剤 | |
| JP7335397B2 (ja) | ２，４，６－トリフルオロ－ｎ－［６－（１－メチル－ピペリジン－４－カルボニル）－ピリジン－２－イル］－ベンズアミドの組成物 | |
| JP2003523324A (ja) | 組合せ医薬および胃腸疾患の処置へのそれらの使用 | |
| AU2013248685A1 (en) | Orally available pharmaceutical formulation suitable for improved management of movement disorders | |
| JP2007518755A (ja) | モノアミン神経伝達物質再取り込み阻害剤及びｎ−メチル−ｄ−アスパラギン酸（ｎｍｄａ）受容体アンタゴニストを含む医薬組成物 | |
| JPH11501282A (ja) | コリン受容体作用薬及び拮抗薬としてのエピバチジン及びその誘導体 | |
| TW200810792A (en) | Immediate-release tablet formulations of a thrombin receptor antagonist | |
| JP2007145869A (ja) | 心房細動の予防または治療のための薬物の製造における５ｈｔ４受容体アンタゴニストの使用 | |
| AU4303400A (en) | Use of saredutant and of its pharmaceutically acceptable salts for the preparation of medicinal products that are useful in the treatment or prevention of major depressive disorders | |
| EP1727547A1 (en) | Compounds for the sustained reduction of body weight | |
| AU782863B2 (en) | The use of 5HT4 receptor antagonists in the prophylaxis or treatment of certain cardiovascular conditions | |
| AU782870B2 (en) | The use of 5HT4 receptor antagonists in the prophylaxis or treatment of certain cardiovascular conditions | |
| AU2005203196B9 (en) | The use of 5HT4 receptor antagonists in the prophylaxis or treatment of certain cardiovascular conditions | |
| EP1755602A1 (en) | Monoamine neurotransmitter re-uptake inhibitor for the inhibition of beta-amyloid (a beta 40 and a beta 42) generation | |
| TWI298022B (en) | Pharmaceutical compositions for the prophylaxis or treatment of atrial remodeling or atrial fibrillation | |
| US20080139615A1 (en) | Combination of a hypnotic agent and r (+)-alpha-(2,3-dimethoxy-phenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol and therapeutic application thereof | |
| TW202448437A (zh) | 米爾維仙(milvexian)於治療及預防患有心房震顫之患者之血栓病況的用途 | |
| CN101297807A (zh) | 5-ht4受体拮抗剂在预防或治疗某些心血管疾病中的应用 | |
| MXPA06008205A (en) | Compounds for the sustained reduction of body weight | |
| HK1123500A (en) | Comination of a hypnotic agent and r(+)-alpha-(2,3-dimethoxy-phenyl)-1-[2-(4-fluorophenl)ethyl]-4-piperidinemethanol and therapeutic application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20060912 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20061212 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20061219 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070312 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20070706 |
|
| RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20070706 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20070706 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20081014 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090206 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20090325 |
|
| A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20090417 |