N-methyl-D-aspartate (NMDA)-mediated muscle relaxant action of dextromethorphan in rats

The present study examined whether the antitussive agent dextromethorphan, which is an antagonist at the N-methyl-D-aspartate (NMDA) receptor, depresses spinal reflexes in rats. Injection of both the specific NMDA antagonist (-)-2-amino-7-phosphonoheptanoate and of dextromethorphan dose-dependently reduced the magnitude of the polysynaptic flexor reflex without affecting the monosynaptic H-reflex. In contrast, the non-NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione depressed the H-reflex in a dose-dependent manner without affecting the flexor reflex. The depressant effect of dextromethorphan on the flexor reflex was prevented by co-administration with NMDA but not with the non-NMDA agonist alpha-amino-3-hydroxy-5-terthyl-4-isoxazole-propionic acid. These data suggest that dextromethorphan exerts a muscle relaxant action via the NMDA receptor.