Nitrendipine: An Antidote to Cardiac and Lethal Toxicity of Cocaine

Abstract

Nitrendipine, a ca²⁺ modulator was tested in the rat as an antagonist to the cardiac toxicity of cocaine and as an antidote to the acute lethal effects of this drug. In a first series of experiments, nitrendipine (1.46 x 10^-3 mg/kg/min) when simultaneously administered intraarterially with cocaine (2 mg/kg/min) suppresses the arrhythmias induced by cocaine and increases survival time from 73 ± 33 min to 309 ± 118 min and the lethal dose of cocaine from 146 ± 66 mg/kg to 618 ± 236 mg/kg (p < 0.003). Nitrendipine also protects the heart from the acute morphological lesions induced by cocaine administration and antagonizes some of the central effects of cocaine. In a second series, 5 rats administered 60 mg/kg of cocaine intraperitoneally had a survival time of 8′ 06 ± 5′ 20 Death was attributed to convulsions and respiratory arrest. Animals treated with nitrendipine (129 x 23 mg/kg) 4′ 30″ after cocaine administration survived. Nitrendipine appears to have general protective effects against cocaine cardiac toxicity and the acute lethal effects of this alkaloid.