Absence of blocking effects on cardiac slow calcium channels by the intracellular calcium antagonist 2-n-propyl-3-dimethylamino-5,6-methylenedioxyindene

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Abstract
Extensive pharmacological evidence supports the contention that 2-n-propyl-3-dimethylamino-5,6-methylenedioxyindene hydrochloride (pr-MDI) is a Ca antagonist with a predominantly intracellular site of action. Electrophysiological evidence points to a possible membrane slow inward Ca channel-blocking property of this agent. To gain further insight as to the site of action of pr-MDI, the interactions between the negative inotropic action of this agent and the positive inotropic actions of excess extracellular Ca (which directly penetrates the myocardial cells through the slow Ca channels), isoproterenol (which indirectly augments Ca influx through the slow Ca channels) and ouabain (which enhances Ca influx through membrane Ca entry routes distinct from the slow Ca channels) were investigated in the isolated, electrically driven guinea pig left atrium. Although excess extracellular Ca, isoproterenol and ouabain reversed the negative inotropic effect of pr-MDI, an analysis of the concentration-response relationships to all 3 positive inotropic agents in the presence and the absence of pr-MDI demonstrated that this agent did not significantly inhibit the contractile effects of Ca, isoproterenol or ouabain at pr-MDI concentrations which exhibit intrinsic negative inotropic effects. Evidently, pr-MDI does not block the membrane slow inward Ca channel or other presumptive membrane routes of Ca entry into myocardial cells at concentrations of .ltoreq. 10-4 M. At very high concentrations (3 .times. 10-4 M) some inhibition of slow channel Ca influx may occur.

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