PHARMACOLOGICAL MECHANISMS IN COCAINE CARDIOVASCULAR EFFECTS

The squirrel monkey is a reliable model for the cardiovascular effects of cocaine in that it mimics the human response to cocaine; low to mo derate doses of cocaine produce a sustained pressor effect and tachyca rdia. Pretreatment experiments have indicated the importance of alpha- 1 and beta-1 adrenoceptor mechanisms in mediating the pressor and tach ycardiac effects of cocaine, respectively. Little support for a role o f dopaminergic mechanisms in the hemodynamic effects of cocaine has be en found. Toxicity to cocaine is often observed hours after its admini stration, pointing to a potential role of the cocaine metabolites. Stu dies on the direct effects and therefore these differing effects of th e metabolites should be considered when evaluating the cardiovascular toxicity of cocaine. Further, as these metabolites are present in the body for long periods of time, these results suggest a role of the met abolites in producing toxicity long after cocaine administration. Fina lly, studies using both dopaminergic and calcium channel antagonists i ndicate that the pharmacological mechanisms involved in the cardiovasc ular effects of cocaine are not the same as those involved in its beha vioral effects.