INHIBITION OF CYTOCHROME P450-DEPENDENT MONOOXYGENASES BY AN ALKALOIDFRACTION FROM HELIETTA-APICULATA MARKEDLY POTENTIATE THE HYPNOTIC ACTION OF PENTOBARBITAL

Crude alkaloid fraction (CAF) isolated from the leaves of Helietta api culata showed the presence of furoquinolines. The extract was investig ated to determine if it can enhance the sensitivity of the central ner vous system (CNS) to the hypnotic action of pentobarbital. Administrat ion of CAF to mice in a dose range of 300-500 mg/kg prior to an inject ion of pentobarbital (40 mg/kg, i.p.) was associated with a statistica lly significant decrease of sleep latency and prolongation of pentobar bital-induced sleeping time. Pretreatment of rats with the same alkalo id extract (150 mg/kg, i.p. for 4 days) prior to administration of pen tobarbital (40 mg/kg, i.p.) caused not only significant reduction of t he levels of microsomal proteins, total cytochrome P450 enzymes and a decrease of aminopyrin-N-demethylation and 3,4-benz(a)pyrene hydroxyla tion but also changed the pattern of cytochrome P450. It is concluded that the CAF isolated from H. apiculata can potentiate the CNS depress ant effect of pentobarbital due to alteration of barbiturate metabolis m through inhibition, mainly, of cytochrome P450-dependent enzymes. (C ) 1998 Elsevier Science Ireland Ltd. All rights reserved.