Nitrendipine: an antidote to cardiac and lethal toxicity of cocaine.
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 less than 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 +/- 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.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000633:toxicity*; D004347:Drug Interactions; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D009568:Nitrendipine / Q000627:therapeutic use*; D051381:Rats; D013997:Time Factors
D009568:Nitrendipine; D003042:Cocaine