Catecholamines,Cocaine Toxicity,and Their Antidotes in the Rat 1

Abstract

Acute lethal cocaine intoxication in the rat induces significant increases of plasma dopamine, norepinephrine, and epinephrine concentrations associated with cardiac functional and morphologic changes. Nitrendipine (a calcium channel antagonist) administered 5 min following cocaine administration lowers catecholamine concentration and restores cardiovascular function to normal, while preventing lethality, and so does enalaprilat (an enzyme-converting inhibitor) administration with diazepam. Cocaine cardiac toxicity in the rat appears to be associated with a significant stimulation of the sympathoadrenal and a sustained elevated plasma concentration of epinephrine. The renin angiotensin system also appears to be activated.