TY - JOUR
T1 - Dextromethorphan attenuates trimethyltin-induced neurotoxicity via σ1 receptor activation in rats
AU - Shin, Eun Joo
AU - Nah, Seung Yeol
AU - Chae, Jong Seok
AU - Bing, Guoying
AU - Shin, Seung Woo
AU - Yen, Tran Phi Hoang
AU - Baek, In Hyuk
AU - Kim, Won Ki
AU - Maurice, Tangui
AU - Nabeshima, Toshitaka
AU - Kim, Hyoung Chun
N1 - 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.
PY - 2007/5
Y1 - 2007/5
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neuint.2007.01.008
DO - 10.1016/j.neuint.2007.01.008
M3 - Article
C2 - 17386960
AN - SCOPUS:34248181123
SN - 0197-0186
VL - 50
SP - 791
EP - 799
JO - Neurochemistry International
JF - Neurochemistry International
IS - 6
ER -