FURAZOLIDONE‐PETHIDINE INTERACTION IN RABBITS

Abstract

The intravenous injection of pethidine in rabbits pretreated with furazolidone administered orally but not systemically resulted in severe interaction and fatal hyperpyrexia. Treatment with p‐chlorophenylalanine, chloropromazine or cyproheptadine protected the rabbits against the furazolidone‐pethidine interaction, while α‐methyl‐p‐tyrosine was ineffective. 5‐Hydroxytryptophan produced a fatal hyperpyrexia in furazolidone pretreated rabbits. Pretreatment of rabbits with 1,1,1‐trichloro‐2, 2‐bis(p‐chlorophenyl)ethane (DDT) accelerated and enhanced the furazolidone‐pethidine interaction, while oxytetracycline pretreatment completely prevented the interaction. It is concluded that furazolidone‐pethidine interaction might depend mainly on potentiation of the effects of 5‐hydroxytryptamine in the CNS and that the transformation of furazolidone into an active monoamine oxidase inhibitor metabolite might occur mainly in the gut microflora in the gut lumen. 1975 British Pharmacological Society