GENETIC AND ENVIRONMENTAL-INFLUENCES ON N EUROMODULATION AND THE ANTINOCICEPTIVE EFFECT OF DEXTROMETHORPHAN

Administration of NMDA antagonists leads to attenuation or disappearan ce of some symptoms of central sensitization, such as secondary hypera lgesia. However, the side effects of NMDA antagonists to a large exten t counterbalance the expected benefits, thus preventing wide or prolon ged use. Dextromethorphan and its metabolite dextrophan, on the other hand, are established and safe drugs. Experimentally they both antagon ize the NMDA receptor. This study evaluates the effects of dextrometho rphan and its metabolite in pain models using electrical stimulation f or testing the antinociceptive effect and capsaicin-induced hyperalges ia. Dextromethorphan shows clear antinociceptive as well as neuromodul ary effects, both depending heavily on the cytochrome P450 2D6 phenoty pe (CYP2D6).