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Published on: September 10, 2018
Behavioural effects of norpethidine, a metabolite of pethidine, in rats
J L Plummer1, G K Gourlay, P L Cmielewski
1Department of Anaesthesia and Intensive Care, Flinders Medical Centre, Bedford Park, South Australia.
Abstract:
This study investigated behavioural effects of the toxic pethidine metabolite, norpethidine, in rats and its interactions with reserpine, apomorphine and physostigmine. Following intraperitoneal administration, brain concentrations of norpethidine reached a plateau after 20-40 min 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 norpethidine, or of apomorphine or physostigmine 15 min after norpethidine, did not alter the norpethidine-induced behaviours; neither did norpethidine block the effects of apomorphine or physostigmine. The characteristic profile of behaviours induced by norpethidine make this toxicant readily amenable to animal studies. Our results indicate that its mechanism of action is unlikely to involve dopaminergic or cholinergic pathways.
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