PHARMACOLOGICAL EVALUATION OF NEW CALCIUM ANTAGONISTS - 2-SUBSTITUTED 3-DIMETHYLAMINO-5,6-METHYLENEDIOXYINDENES - EFFECTS ON ISOLATED HEARTS AND CORONARY VESSELS

  • 1 January 1979
    • journal article
    • research article
    • Vol. 210  (1) , 141-146
Abstract
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 Ca 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 .times. 10-6 to 10-4 M) produced a concentration-dependent relaxation of K-contracted strips of bovine extramural coronary vessels, which was reversible upon elevation of the Ca concentration in the medium. In the nonstimulated isolated perfused rabbit heart, the 2-n-propyl aminoindene (3 .times. 10-5 M) and the 2-n-butyl aminoindene (3 .times. 10-5 and 10-4 M) increased coronary flow without affecting cardiac chronotropic activity. The 2-n-propyl aminoindene (3 .times. 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.