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 language | English |
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Pages (from-to) | 791-799 |
Number of pages | 9 |
Journal | Neurochemistry International |
Volume | 50 |
Issue number | 6 |
DOIs | |
State | Published - 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.
Funders | Funder number |
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Korean Ministry of Health and Welfare | M103KV010013-06K220201310 |
Ministry of Science and Technology |
Keywords
- Anticonvulsant
- Dextromethorphan
- Trimethyltin
- σ Receptor
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Cell Biology