Effects of cocaine and cocaine metabolites on cardiovascular function in squirrel monkeys

The effects of cocaine and the cocaine metabolites norcocaine, ecgonine methyl ester, benzoylecgonine and cocaethylene were evaluated in conscious squirrel monkeys for their effects on blood pressure and heart rate. Norcocaine, ecgonine methyl ester and benzoylecgonine are produced in vivo following cocaine use. Cocaethylene is produced in vivo following concurrent cocaine and alcohol use. Increases in both blood pressure and heart rate were observed following cocaine doses of 0.3-3.0 mg/kg. Ecgonine methyl ester and benzoylecgonine had no effect on either parameter up to doses of 10.0 mg/kg. Norcocaine increased blood pressure, but was less potent than cocaine. Norcocaine did not affect heart rate at doses up to 3.0 mg/kg. In contrast to the other metabolites, cocaethylene increased blood pressure and heart rate similarly to cocaine. These results suggest that ecgonine methyl ester and benzoylecgonine are devoid of cardiovascular effects at doses comparable to cocaine and would not be expected to contribute to cocaine's overall cardiovascular effects. Norcocaine's effect on blood pressure might contribute to the cardiovascular effects of cocaine, but this metabolite is produced only at low levels in vivo. The one metabolite that might be expected to contribute to cocaine's overall cardiovascular effect is cocaethylene, although the degree of this contribution is not clear.