title: 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: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, South Korea.
authors: Eun-Joo
authors: EJ
authors: Shin
authors: Seung-Yeol
authors: SY
authors: Nah
authors: Jong Seok
authors: JS
authors: Chae
authors: Guoying
authors: G
authors: Bing
authors: Seung Woo
authors: SW
authors: Shin
authors: Tran Phi Hoang
authors: TP
authors: Yen
authors: In-Hyuk
authors: IH
authors: Baek
authors: Won-Ki
authors: WK
authors: Kim
authors: Tangui
authors: T
authors: Maurice
authors: Toshitaka
authors: T
authors: Nabeshima
authors: Hyoung-Chun
authors: HC
authors: Kim
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D003915:Dextromethorphan / Q000494:pharmacology*; D005029:Ethylenediamines / Q000494:pharmacology; D007150:Immunohistochemistry; D007859:Learning Disabilities / Q000139:chemically induced / Q000517:prevention & control / Q000523:psychology; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009410:Nerve Degeneration / Q000139:chemically induced / Q000517:prevention & control; D020258:Neurotoxicity Syndromes / Q000517:prevention & control*; D010880:Piperidines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011916:Rats, Inbred F344; D017478:Receptors, Phencyclidine / Q000187:drug effects; D017480:Receptors, sigma / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced / Q000523:psychology; D014298:Trimethyltin Compounds / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000097605:Sigma-1 Receptor
chemical_list: D000317:Adrenergic alpha-Antagonists; D003915:Dextromethorphan; D005029:Ethylenediamines; D010880:Piperidines; D017478:Receptors, Phencyclidine; D017480:Receptors, sigma; D014298:Trimethyltin Compounds; D000097605:Sigma-1 Receptor; C046488:trimethyltin; C097963:N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin; C010739:ifenprodil