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Nitrendipine as an Antagonist to the Cardiac Toxicity of Cocaine
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1987
Year
Isolated HeartCocaine AdministrationCardiovascular PharmacologyPharmacotherapyExperimental PharmacologyMolecular PharmacologyCardiac ToxicityDrug MonitoringPulse PressureCardiologyAnesthetic PharmacologyDrug ToxicityHealth SciencesPsychoactive DrugBehavioral PharmacologyPharmacologySubstance AbuseCardiovascular DiseaseAddictionPhysiologyClinical PharmacologyCardiovascular PharmacodynamicsMedicine
Cocaine (10−7–10−4) administered to the isolated heart increases rate in the presence of a stable or decreased coronary flow, while pulse pressure is not consistently altered. Arrhythmias and irreversible cardiac impairment occur with concentrations exceeding 10−4M. While propranolol does not alter these effects, nitrendipine (10−7M), simultaneously administered with the same range of cocaine concentration, decreases tachycardia and increases pulse pressure and coronary flow. In the intact rat, nitrendipine (1.46 × 10−3 mg/kg/min), when simultaneously administered intra-arterially 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 increases from 146 ± 66mg/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.