Interaction between dextromethorphan and norpethidine in rats.
With increasing interest in the application of dextromethorphan in pain control, it is probable that patients will receive this drug in combination with analgesics such as opioids, giving rise to the potential for previously unobserved drug interactions. The interaction between dextromethorphan, and its pharmacologically active metabolite dextrorphan, and norpethidine, a toxic metabolite of pethidine, was examined in rats. Rats were assigned to receive dextromethorphan (0, 20 or 40 mg/kg) or dextrorphan (0, 15 or 30 mg/kg) combined with norpethidine (0, 28 or 42 mg/kg). The occurrence of seizures, myoclonic jerks and shivering was recorded for 60 min after drug administration. Norpethidine produced dose-related increases in the incidence of seizures, myoclonic jerks and shivering. Dextromethorphan, but not dextrorphan, increased the incidence of these behaviours. It is recommended that extreme caution be exercised if dextromethorphan and pethidine are to be used together.
Plummer
J L
JL
Pain Management Unit, Flinders Medical Centre and The Flinders University of South Australia, Bedford Park, Australia.
Tran
K D
KD
Gourlay
G K
GK