Induction of phencyclidine-like behavior in rats by dextrorphan but not dextromethorphan

The behavioral effects of dextromethorphan (DM), dextrorphan (DO) and phencyclidine (PCP) were compared in rats. DO (15-120 mg/kg) was similar to PCP (1.25-20 mg/kg) in inducing dose-dependent locomotor hyperactivity, stereotypy and ataxia. DM (15-120 mg/kg) induced moderate hyperactivity only at the higher doses about 45 min after treatment. DM and DO modified the locomotor facilitation induced by 10 mg/kg PCP in opposite directions. Pretreatment with DO facilitated, whereas DM dose-dependently inhibited PCP-elicited hyperactivity. Although the metabolism of DM in rats is unknown, the recently reported abuse of DM in humans may occur by its conversion to DO in the organism, i.e., to a metabolite which produces PCP-like effects.