Dextrorphan, but not dextromethorphan, exerts weak antidystonic effects in mutant dystonic hamsters.
The effects of dextromethorphan and its metabolite dextrorphan on severity of dystonia were examined in mutant dystonic hamsters, an animal model of idiopathic paroxysmal dystonia, in which recent examinations have shown antidystonic effects of selective N-methyl-D-aspartate (NMDA) receptor antagonists. Dextromethorphan and dextrorphan are non-competitive NMDA receptor antagonists which additionally exhibit affinity for sigma receptors. Dextrorphan (20 and 40 mg/kg i.p.) significantly retarded the progression of dystonia at the higher dose, whereas dextromethorphan (20, 40, 60 mg/kg i.p.) failed to exert any antidystonic effects even at high doses which caused severe effects. The lack of antidystonic efficacy of dextromethorphan may be related to its higher affinity to sigma receptors compared with dextrorphan.
Richter
A
A
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany.
Löscher
W
W
D000818:Animals; D000996:Antitussive Agents / Q000627:therapeutic use*; D006224:Cricetinae; D003915:Dextromethorphan / Q000627:therapeutic use*; D003917:Dextrorphan / Q000627:therapeutic use*; D018450:Disease Progression; D004421:Dystonia / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D017480:Receptors, sigma / Q000187:drug effects / Q000378:metabolism
D000996:Antitussive Agents; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D017480:Receptors, sigma; D003917:Dextrorphan; D003915:Dextromethorphan