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

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.

• Authors: Eun-Joo Shin, Seung-Yeol Nah, Jong Seok Chae, Guoying Bing, Seung Woo Shin, Tran Phi Hoang Yen, In-Hyuk Baek, Won-Ki Kim, Tangui Maurice, Toshitaka Nabeshima, Hyoung-Chun Kim
• Journal: Neurochemistry international (Neurochem Int) Vol. 50 Issue 6 Pg. 791-9 (May 2007) ISSN: 0197-0186 [Print] England
• PMID: 17386960 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic alpha-Antagonists
• Ethylenediamines
• Piperidines
• Receptors, Phencyclidine
• Receptors, sigma
• Trimethyltin Compounds
• trimethyltin
• N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin
• Dextromethorphan
• ifenprodil

Topics

• Adrenergic alpha-Antagonists (pharmacology)
• Animals
• Avoidance Learning (drug effects)
• Behavior, Animal (drug effects)
• Dextromethorphan (pharmacology)
• Ethylenediamines (pharmacology)
• Immunohistochemistry
• Learning Disabilities (chemically induced, prevention & control, psychology)
• Maze Learning (drug effects)
• Memory (drug effects)
• Nerve Degeneration (chemically induced, prevention & control)
• Neurotoxicity Syndromes (prevention & control)
• Piperidines (pharmacology)
• Radioligand Assay
• Rats
• Rats, Inbred F344
• Receptors, Phencyclidine (drug effects)
• Receptors, sigma (drug effects)
• Seizures (chemically induced, psychology)
• Trimethyltin Compounds (antagonists & inhibitors, toxicity)
• Sigma-1 Receptor