THE ROLE OF CATECHOLAMINES IN COCAINE TOXICITY - A MODEL FOR COCAINE SUDDEN-DEATH

Sudden death associated with cocaine abuse is preceded by a state of a gitated delirium. We postulated that release of catecholamines associa ted with this stress enhanced toxicity from cocaine. Thus we investiga ted the effect of catecholamine infusion [(epinephrine (7.25 ugml(-1)) , norepinephrine (4.4 ugml(-1)) and dopamine (8.0 ugml(-1)), infused a t 6 ml h(-1)] on the toxicity from concomitant infusion of cocaine (1 mg-kg(-1)min(-1)). Two groups of rats were studied in order to isolate distinct toxicity endpoints: convulsions and respiratory arrest in co nscious, and, circulatory arrest in anesthetized and ventilated rats. Catecholamines were administered at either full or 1/2 strength to est ablish a dose response effect on cocaine toxicity. Catecholamine infus ion in a dose dependent fashion provoked earlier convulsions and respi ratory arrest in conscious rats and circulatory arrest in anesthetized and ventilated rats. Despite lower cocaine cumulative dose administra tion, rats receiving catecholamines had similar plasma cocaine concent rations at the onset of convulsions and respiratory arrest compared to those with cocaine infusion alone. The data suggest that catecholamin es enhance the convulsive, respiratory and circulatory toxicity of coc aine by a pharmacokinetic interaction.