Indirect stimulatory action of the calcium channel blocker AQA-39

AQA-39 is a new bradycardia-inducing drug chemically related to verapamil that reduces potassium conductance and blocks calcium channels. In canine ventricular trabeculae studied at 25 degrees C and at a pacing rate of 12 stimuli per minute. AQA-39, in concentrations of 1 and 2 X 10(-5) M, had a significant positive (and only positive) inotropic effect. Propranolol significantly diminished this positive inotropic action of AQA-39. After catecholamine depletion with reserpine, AQA-39 still elicited a significant increase in contractility but the magnitude of the increment in contractile performance was considerably less than the one observed when normal muscles were exposed to AQA-39. AQA-39 had no significant inotropic action on reserpinized and atropinized muscles. From these results we can conclude that AQA-39 is not a beta adrenoceptor agonist although adrenergic influences via neuronal norepinephrine release are mediating part of the inotropic effect of the drug. Furthermore, at this low rate of stimulation and at the concentrations used, AQA-39 has no direct inotropic action of its own but part of its indirect stimulatory action is mediated through an antimuscarinic effect.