Pharmacological evaluation of new calcium antagonists: 2-substituted 3-dimethylamino-5,6-methylenedioxyindenes. Effects on isolated hearts and coronary vessels.
The 2-n-propyl and 2-n-butyl aminoindene hydrochlorides were previously reported to interfere with excitation-contraction coupling in uterine and intestinal smooth muscle, and with stimulus-secretion coupling in the adrenal medulla, by interfering with the action of calcium at an intracellular site. The present investigation was designed to apply this knowledge to the potential coronary and cardiac effects of such a pharmacological action. The 2-n-propyl and 2-n-butyl aminoindenes (5 X 10(-6)-10(-4) M) produced a concentration-dependent relaxation of potassium-contracted strips of bovine extramural coronary vessels, which was reversible upon elevation of the calcium concentration in the medium. In the nonstimulated isolated perfused rabbit heart, the 2-n-propyl aminoindene (3 X 10(-5) M) and the 2-n-butyl aminoindene (3 X 10(-5) and 10(-4) M) increased coronary flow without affecting cardiac chronotropic activity. However, the 2-n-propyl aminoindene (3 X 10(-5) and 10(-4)M) and the 2-n-butyl aminoindene (10(-4) M) produced a negative inotropic action in this preparation. The combination of coronary dilation and decreased force of cardiac contraction may represent desirable properties for drugs useful in the treatment of ischemic heart disease.
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors*; D002417:Cattle; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007192:Indenes / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D011299:Prenylamine / Q000494:pharmacology; D011817:Rabbits; D013806:Theophylline / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D007192:Indenes; D013806:Theophylline; D011299:Prenylamine; D011188:Potassium; D002118:Calcium