title: [Genetic and environmental effects on neuromodulation and the antinociceptive effect of dextromethorphan].
abstract: Administration of NMDA antagonists leads to attenuation or disappearance of some symptoms of central sensitization, such as secondary hyperalgesia. However, the side effects of NMDA antagonists to a large extent counterbalance the expected benefits, thus preventing wide or prolonged use. Dextromethorphan and its metabolite dextrophan, on the other hand, are established and safe drugs. Experimentally they both antagonize the NMDA receptor. This study evaluates the effects of dextromethorphan and its metabolite in pain models using electrical stimulation for testing the antinociceptive effect and capsaicin-induced hyperalgesia. Dextromethorphan shows clear antinociceptive as well as neuromodulary effects, both depending heavily on the cytochrome P450 2D6 phenotype (CYP2D6).
authors.affiliation: Division de pharmacologie clinique, Hôpital cantonal universitaire de Genève.
authors.forename: M K
authors.initials: MK
authors.lastname: Oestreicher
authors.forename: J
authors.initials: J
authors.lastname: Desmeules
authors.forename: V
authors.initials: V
authors.lastname: Piguet
authors.forename: A F
authors.initials: AF
authors.lastname: Allaz
authors.forename: P
authors.initials: P
authors.lastname: Dayer
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000493:pharmacokinetics / Q000494:pharmacology*; D000996:Antitussive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D003915:Dextromethorphan / Q000493:pharmacokinetics / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000235:genetics; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D017288:Pain Threshold / Q000187:drug effects*; D010641:Phenotype; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012189:Retrospective Studies; D012931:Social Environment
chemical_list: D000701:Analgesics, Opioid; D000996:Antitussive Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D003915:Dextromethorphan
vernacular_title: Influences génétiques et environnementales sur la neuromodulation et l'effet antinociceptif du dextromethorphan.