Résumé
We showed that dextromethorphan (DM) provides neuroprotective/anticonvulsant effects and that DM and its major metabolite, dextrorphan, have a high-affinity for σ
1 receptors, but a low affinity for σ
2 receptors. In addition, we found that DM has a higher affinity than DX for σ
1 sites, whereas DX has a higher affinity than DM for PCP sites. We extend our earlier findings by showing that DM attenuated trimethyltin (TMT)-induced neurotoxicity (convulsions, hippocampal degeneration and spatial memory impairment) in rats. This attenuation was reversed by the σ
1 receptor antagonist BD 1047, but not by the σ
2 receptor antagonist ifenprodil. DM attenuates TMT-induced reduction in the σ
1 receptor-like immunoreactivity of the rat hippocampus, this attenuation was blocked by the treatment with BD 1047, but not by ifenprodil. These results suggest that DM prevents TMT-induced neurotoxicity, at least in part, via σ
1 receptor stimulation.