Effects of the novel calcium channel blocker, anipamil, on the isolated rabbit heart. Comparison with verapamil and gallopamil.

The calcium channel blocking activity of the novel phenylalkylamine derivative, anipamil, was tested on the isolated rabbit heart, in comparison with verapamil and gallopamil. Anipamil and the other calcium channel blockers lower left ventricular pressure in the same concentration range (10(-8)-10(-4) mol/l). The negative inotropic effect of anipamil is only partially reversed (nearly 65%) by rising calcium concentration in the perfusion fluid, whilst a complete recovery is observed for verapamil and gallopamil. The negative inotropic effect of anipamil is of rapid onset but long lasting, being still present 12 h after washout. On the contrary, that of gallopamil or verapamil completely disappears within 3 h of washout. Verapamil and gallopamil (10(-8)-10(-4) mol/l) depress spontaneous heart rate up to asystolia and abolish the vasopressin- and Bay K 8644-induced coronary spasm. Anipamil, on the contrary, does not modify coronary spasm elicited by both stimulants and spontaneous heart rate up to 10(-4) mol/l. These observations suggest that anipamil, in the isolated rabbit heart, possesses a peculiar pharmacological profile, since its calcium channel blocking activity is confined to the myocardial muscle.