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  • 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.
    Author: Ueda M, Matsumura S, Masui M, Matsuura E, Uno O, Kawakami M, Ninomiya M, Adachi I.
    Journal: Arzneimittelforschung; 1993 Dec; 43(12):1270-5. PubMed ID: 8141813.
    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.
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