Antiparkinsonian action of dextromethorphan in the reserpine-treated mouse

Dextromethorphan has been reported to be a weak antagonist of the ion channel associated with the NMDA receptor, and to have putative antiparkinsonian activity in man. This study looked at the effects of dextromethorphan in normal and monoamine-depleted mice, to determine whether it exhibited a behavioural profile with regard to motor activity that was consistent with NMDA receptor blockade. In normal mice, 5-80 mg/kg i.p. dextromethorphan caused modest muscle relaxation at the highest dose in all animals; hyperlocomotion and stereotypy were evident at 40 mg/kg i.p. in a fraction of mice (4/14). In 24 h reserpine-treated mice, locomotion was reinstated by the dopamine D1 receptor agonist 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride (SKF 38393, 30 mg/kg i.p.), the dopamine D2 receptor agonist N-n-propyl-N-phenylethyl-p-(3-hydroxyphenyl)ethylamine (RU 24213, 5 mg/kg s.c.) and L-3,4-dihydroxyphenylalanine (L-DOPA, 150 mg/kg i.p. in conjunction with benserazide 100 mg/kg i.p.). Dextromethorphan alone (10-40 mg/kg i.p.) caused non-significant arousal of monoamine-depleted mice, but potentiated synergistically movements elicited by SKF 38393 and L-DOPA, though not RU 24213. The possible use of dextromethorphan as an adjunct to L-DOPA in the treatment of Parkinson's disease in man, is discussed.