Dextromethorphan attenuates trimethyltin-induced neurotoxicity via sigma1 receptor activation in rats.

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Shin EJ, Nah SY, Chae JS, Bing G, Shin SW, Yen TP, Baek IH, Kim WK, Maurice T, Nabeshima T, Kim HC

Dextromethorphan attenuates trimethyltin-induced neurotoxicity via sigma1 receptor activation in rats.

Neurochem Int. 2007 May;50(6):791-9. Epub 2007 Feb 4.

PubMed ID

17386960 [ View in PubMed

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Abstract

We showed that dextromethorphan (DM) provides neuroprotective/anticonvulsant effects and that DM and its major metabolite, dextrorphan, have a high-affinity for sigma(1) receptors, but a low affinity for sigma(2) receptors. In addition, we found that DM has a higher affinity than DX for sigma(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 sigma(1) receptor antagonist BD 1047, but not by the sigma(2) receptor antagonist ifenprodil. DM attenuates TMT-induced reduction in the sigma(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 sigma(1) receptor stimulation.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Dextromethorphan	Sigma non-opioid intracellular receptor 1	Protein	Humans	Yes	Agonist	Details