title: Pharmacological studies on a new dihydrothienopyridine calcium antagonist. 1st communication: comparative studies on the cardiovascular effects of methyl-4,7-dihydro-3-isobutyl-6-methyl-4-(3-nitrophenyl)thieno[2,3- b]pyridine-5-carboxylate and its two enantiomers in experimental animals.
abstract: Antihypertensive effects in conscious spontaneously hypertensive rats (SHR), cardiovascular effects in anesthetized dogs, and calcium antagonistic effects in the rabbit isolated basilar arteries and guinea-pig isolated coronary arteries of S-312 (methyl-4,7-dihydro-3-isobutyl-6-methyl-4- (3-nitrophenyl) thieno [2,3-b] pyridine-5-carboxylate) and its two enantiomers were comparatively investigated. The antihypertensive effect in SHR and hypotensive effect in anesthetized dogs of S-312-d (CAS 120056-57-7) were approximately 2 times more potent than those of S-312, but these effects of S-312-l were very weak even at 10 to 100 times higher doses. Increases of vertebral blood flow in dogs with S-312 and S-312-d were almost corresponding. The IC50 concentrations of S-312-d, S-312, S-312-l in the rabbit isolated basilar arteries contracted with high K+ solution were 1.4 x 10(-10) mol/l, 2.2 x 10(-10) mol/l, and 4.6 x 10(-9) mol/l, respectively. The relaxing effect of S-312-d in the isolated coronary arteries was most potent, followed by those of S-312 and S-312-l. It is concluded that the cardiovascular and calcium antagonistic effect of S-312-d are mainly responsible for those effects of S-312.
authors.affiliation: Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ueda
authors.forename: S
authors.initials: S
authors.lastname: Matsumura
authors.forename: M
authors.initials: M
authors.lastname: Masui
authors.forename: E
authors.initials: E
authors.lastname: Matsuura
authors.forename: O
authors.initials: O
authors.lastname: Uno
authors.forename: M
authors.initials: M
authors.lastname: Kawakami
authors.forename: M
authors.initials: M
authors.lastname: Ninomiya
authors.forename: I
authors.initials: I
authors.lastname: Adachi
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001488:Basilar Artery / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D012039:Regional Blood Flow / Q000187:drug effects; D013237:Stereoisomerism
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C059447:S 312