Hepatic drug-metabolizing enzyme activity in rats pretreated with (-)-emetine or (plus or minus)-2,3-dehydroemetine.
1. Pretreatment of female rats with (-)-emetine or (+/-)-2,3-dehydroemetine (at 18mumol/kg body wt. for 24h) prolongs the hexobarbital-induced sleeping-time of the treated animals. 2. This effect is not observed on pretreating animals with other compounds closely related to (-)-emetine, such as (-)-isoemetine or (+)-O-methylpsychotrine. 3. Liver microsomal drug-metabolizing enzyme activity in vitro as measured by N-demethylation of aminopyrine and azo-reduction of Neoprontosil is inhibited in rats pretreated with (-)-emetine or with (+/-)-2,3-dehydroemetine. 4. These inhibitory effects on drug metabolism in vitro are not observed in corresponding experiments involving pretreatment of rats with (-)-isoemetine or (+)-O-methylpsychotrine. 5. Co-administration of emetine or 2,3-dehydroemetine and sodium phenobarbital or 1,1-dichloro-2-o-chlorophenyl-2-p-chlorophenylethane to rats abolishes or greatly diminishes the stimulation of drug-metabolizing enzyme activity in vitro usually obtained by the administration of phenobarbital or 1,1-dichloro-2-o-chlorophenyl-2-p-chlorophenylethane alone. 6. Further, in rats pretreated with sodium phenobarbital and subsequently injected with emetine or 2,3-dehydroemetine the pre-stimulated drug-metabolizing enzyme activity in vitro is diminished. 7. The inhibitory effects on drug-metabolizing enzyme activity after pretreatment with (-)-emetine or (+/-)-2,3-dehydroemetine do not appear to be related to NADPH generation.
D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D003864:Depression, Chemical; D004357:Drug Synergism; D004640:Emetine / Q000494:pharmacology*; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors; D006591:Hexobarbital / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D009249:NADP / Q000096:biosynthesis; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D013449:Sulfonamides / Q000378:metabolism
D013449:Sulfonamides; D000632:Aminopyrine; D009249:NADP; D006591:Hexobarbital; D005954:Glucosephosphate Dehydrogenase; D004640:Emetine; D010634:Phenobarbital