Certain clinically-utilized antibiotics enhance the behavioural effects ofcocaine

Cytochrome P-450s (CYPs) belonging to subfamilies 2B and 3A are the major C YPs involved in the N-demethylation of cocaine in the rat. However, the eff ects of inhibitors of these enzymes on the behavioural actions of cocaine a re unknown. Hence, the effects of the CYP 3A inhibitors troleandomycin and erythromycin, and the CYP 2B (and 3A) inhibitor chloramphenicol, were exami ned on the locomotor activating effects of cocaine (20 mg/kg i.p). Troleand omycin, chloramphenicol and erythromycin all potentiated the locomotor acti vating effects of cocaine, although the effect was only statistically signi ficant for the first two drugs. Since variation exists in the human populat ion with respect to the catalytic activity of CYP 3A isozymes, which are th e principal cocaine N-demethylators in humans, inhibition of CYP 3A by trol eandomycin in the rat may be useful as a model of the human cocaine "poor m etabolizer" phenotype.