Certain clinically-utilized antibiotics enhance the behavioural effects of cocaine.
Abstract Cytochrome P-450s (CYPs) belonging to subfamilies 2B and 3A are the major CYPs involved in the N -demethylation of cocaine in the rat. However, the effects of inhibitors of these enzymes on the behavioural actions of cocaine are unknown. Hence, the effects of the CYP 3A inhibitors troleandomycin and erythromycin, and the CYP 2B (and 3A) inhibitor chloramphenicol, were examined on the locomotor activating effects of cocaine (20 mg/kg i.p.). Troleandomycin, chloramphenicol and erythromycin all potentiated the locomotor activating effects of cocaine, although the effect was only statistically significant for the first two drugs. Since variation exists in the human population with respect to the catalytic activity of CYP 3A isozymes, which are the principal cocaine N -demethylators in humans, inhibition of CYP 3A by troleandomycin in the rat may be useful as a model of the human cocaine "poor metabolizer" phenotype.
Overton
P G
PG
Department of Psychology, University of Wales Swansea, Swansea, UK.
Marrow
L P
LP
Brain
P F
PF
Clark
D
D