BEHAVIORAL-EFFECTS OF NORPETHIDINE, A METABOLITE OF PETHIDINE, IN RATS

This study investigated behavioural effects of the toxic pethidine met abolite, norpethidine, in rats and its interactions with reserpine, ap omorphine and physostigmine. Following intraperitoneal administration, brain concentrations of norpethidine reached a plateau after 20-40 mi n and remained elevated for 2 h. In the dose range 0.06-0.18 mmol/kg, norpethidine induced myoclonic jerks, a characteristic splayed posture , and episodes of exaggerated shivering. Forward locomotion, grooming, yawning and rearing were suppressed. Seizures and reverse locomotion occurred occasionally. Administration of reserpine 1 h prior to norpet hidine, or of apomorphine or physostigmine 15 min after norpethidine, did not alter the norpethidine-induced behaviours; neither did norpeth idine block the effects of apomorphine or physostigmine. The character istic profile of behaviours induced by norpethidine make this toxicant readily amenable to animal studies. Our results indicate that its mec hanism of action is unlikely to involve dopaminergic or cholinergic pa thways.