effect of some neuroleptic and tranquilizing agents on the liver drug metabolizing enzymes and mitochondrial ATPase activity

ABSTRACT

Treatment of rats for three successive days with bromazepam, loxapine and diazepam in doses of 5, 10, and 20 mg/kg body weight, respectively, caused a marked increase in microsomal drug-metabolizing enzyme activity involved in N-demethylation and aromatic p-hydroxylation. In addition, these drugs significantly decreased the sleeping time of animals induced by hexabarbital [100 mg/kg. I.P.]. Sulpiride, a neuroleptic agent, at a dose of 15 mg/kg, I.P. was without effect on both the microsomal drug-metabolizing enzymes and the hexobarbital sleeping time. With regards to the effect of these drugs on mitochondrial energetics, bromazepam [0.1 mM] and diazepam [0.1 mM] significantly inhibited ATPase activity, loxapine [0.1 mM] stimulated ATPase activity and decreased ADP O ratio, whereas sulpiride was without effect. The significance of these results was discussed