Dextromethorphan attenuates trimethyltin-induced neurotoxicity via σ1 receptor activation in rats

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

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

We showed that dextromethorphan (DM) provides neuroprotective/anticonvulsant effects and that DM and its major metabolite, dextrorphan, have a high-affinity for σ1 receptors, but a low affinity for σ2 receptors. In addition, we found that DM has a higher affinity than DX for σ1 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 σ1 receptor antagonist BD 1047, but not by the σ2 receptor antagonist ifenprodil. DM attenuates TMT-induced reduction in the σ1 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 σ1 receptor stimulation.

Original languageEnglish
Pages (from-to)791-799
Number of pages9
JournalNeurochemistry International
Volume50
Issue number6
DOIs
StatePublished - May 2007

Bibliographical note

Funding Information:
This study was supported by a grant of the Korea Health 21 R&D Project (A020007), Ministry of Health & welfare, Republic of Korea, by a grant (M103KV010013-06K220201310) from the Brain Research Center from the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea, and by Brain Korea 21 project. Equipments at the Institute of Pharmaceutical Science (Kangwon National University) and Korea Basic Science Institute, Chunchon center (Chunchon, South Korea) were used for this study.

Funding

This study was supported by a grant of the Korea Health 21 R&D Project (A020007), Ministry of Health & welfare, Republic of Korea, by a grant (M103KV010013-06K220201310) from the Brain Research Center from the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea, and by Brain Korea 21 project. Equipments at the Institute of Pharmaceutical Science (Kangwon National University) and Korea Basic Science Institute, Chunchon center (Chunchon, South Korea) were used for this study.

FundersFunder number
Korean Ministry of Health and WelfareM103KV010013-06K220201310
Ministry of Science and Technology

    Keywords

    • Anticonvulsant
    • Dextromethorphan
    • Trimethyltin
    • σ Receptor

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience
    • Cell Biology

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