PHARMACOLOGICAL EVALUATION OF NEW CALCIUM ANTAGONISTS-2-SUBSTITUTED 3-DIMETHYLAMINO-5,6-METHYLENEDIOXYINDENES

  • 1 January 1977
    • journal article
    • research article
    • Vol. 201  (1) , 126-137
Abstract
Two 2-substituted 3-dimethylamino-5,6-methylenedioxyindene hydrochlorides were tested for antagonism of the spasmogenic action of various agonists on isolated smooth muscle preparations. The 2-n-propyl and 2-n-butyl aminoindenes (5 .times. 10-5 to 10-4 M) blocked the spasmogenic action on the estrogen-treated rat uterus of prostaglandin[PG]E2 (10-7 M), PGF2.alpha. tromethamine salt (10-7 M), oxytocin (10-3 U[units]/ml), BaCl2 (BaCl2 .cntdot. 2H2O; 2.2 .times. 10-4 M), acetylcholine chloride (10-6 M) and ergonovine maleate (7.5 .times. 10-4 M); they also blocked the contractile effect on the ileum of acetylcholine chloride (10-6 M; rat) and histamine hydrochloride (10-6 M; guinea pig). In further experiments on rat uterus using the agonists acetylcholine chloride (10-6 M; which presumably acts by increasing influx of extracellular Ca into cells) and BaCl2 (2.2 .times. 10-4 M; which presumably contracts smooth muscle by releasing intracellular Ca), a progressive increase in extracellular Ca concentration (from 9 .times. 10-4 to 7.2 .times. 10-3 M CaCl2 .cntdot. 2H2O) was paralleled by progressive reversal of the blockade produced by both 2-substituted aminoindene antagonists. In studies on the perfused bovine adrenal medulla, the 2-n-propyl aminoindene (10-4 M) completely blocked the Ca-dependent catecholamine secretion evoked by 0.1 and 3.3 mM carbachol, without affecting the Ca-independent catecholamine secretion evoked by 33 mM acetaldehyde. The aminoindene antagonists interfered with the action of Ca and in smooth muscle the antagonism was at an intracellular site involved in excitation-contraction coupling.