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.
Block
F
F
Dept. of Neurology, University of Essen, Germany.
Schwarz
M
M
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology; D003915:Dextromethorphan / Q000008:administration & dosage / Q000494:pharmacology*; D004558:Electric Stimulation; D004576:Electromyography / Q000187:drug effects; D006181:H-Reflex / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009132:Muscles / Q000187:drug effects*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012026:Reflex, Stretch / Q000187:drug effects
D000596:Amino Acids; D000927:Anticonvulsants; D011810:Quinoxalines; C056723:FG 9041; D016202:N-Methylaspartate; D003915:Dextromethorphan; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid