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

doi:10.1016/j.neuint.2007.01.008

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 journal › Article › peer-review

40 Citations (Scopus)

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
Pages (from-to)	791-799
Number of pages	9
Journal	Neurochemistry International
Volume	50
Issue number	6
DOIs	https://doi.org/10.1016/j.neuint.2007.01.008
Publication status	Published - 2007 May
Externally published	Yes

Keywords

Anticonvulsant
Dextromethorphan
Trimethyltin
σ Receptor

ASJC Scopus subject areas

Cellular and Molecular Neuroscience
Cell Biology

Access to Document

10.1016/j.neuint.2007.01.008

Cite this

@article{b3f3d233e01042c1b41bbd921d8c25c4,

title = "Dextromethorphan attenuates trimethyltin-induced neurotoxicity via σ1 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 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.",

keywords = "Anticonvulsant, Dextromethorphan, Trimethyltin, σ Receptor",

author = "Shin, {Eun Joo} and Nah, {Seung Yeol} and Chae, {Jong Seok} and Guoying Bing and Shin, {Seung Woo} and Yen, {Tran Phi Hoang} and Baek, {In Hyuk} and Kim, {Won Ki} and Tangui Maurice and Toshitaka Nabeshima and Kim, {Hyoung Chun}",

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.",

year = "2007",

month = may,

doi = "10.1016/j.neuint.2007.01.008",

language = "English",

volume = "50",

pages = "791--799",

journal = "Neurochemistry International",

issn = "0197-0186",

publisher = "Elsevier Limited",

number = "6",

}

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.

KW - Anticonvulsant

KW - Dextromethorphan

KW - Trimethyltin

KW - σ Receptor

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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 -