Inhibition of the metabolism of cocaine by SKF-525A.

In vitro and in vivo studies in rats indicate cocaine to be metabolized primarily in the liver to form benzoylecgonine and norcocaine. The formation of these metabolites was significantly hindered by SKF-525A, a microsomal enzyme inhibitor. In in vivo studies, pretreatment of rats with SKF-525A prior to receiving cocaine resulted in increased amounts of unchanged cocaine in the brain. No accompanying increase in spontaneous motor activity was observed for these animals, indicating a possible role for metabolites in the stimulant action of cocaine.