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.
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.
Ueda
M
M
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Matsumura
S
S
Masui
M
M
Matsuura
E
E
Uno
O
O
Kawakami
M
M
Ninomiya
M
M
Adachi
I
I
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
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C059447:S 312