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ID 14118
Eprint ID
14118
FullText URL
Thumnail 103_749.pdf 6.38 MB
Title Alternative
Role of sigma sites in the modulation of neuroleptics-induced dystonia in rats
Author
Okumura, Kazuya
Abstract
Recent findings have suggested that neuroleptics exhibit a strong affinity for not only dopamine receptors, but also the sigma sites. Therefore, some clinical or adverse effects of neuroleptics may be due to their action on the sigma sites. This study showed that intrarubral microinjection of 1,3-di-o-tolylguanidine (DTG) or (+) -3- (3-hydroxyphenyl) -N-1-propyl) piperidine, sigma ligands, and several neuroleptics such as haloperidol caused dystonic reactions in rats resembling tha acute dystonic reaction in humans. The intensity and duration of the dystonia induced by these drugs showed a correlation with their affinities for the sigma sites. These findings raise the possibility that the acute dystonic reaction, one of the motor side effects of neuroleptics, might be mediated via the sigma sites. On the other hand, BMY 14802, an atypical neuroleptic, never caused dystonia after intrarubral microinjection. Furthermore, BMY 14802 still inhibited the dystonia induced by intrarubral microinjection of DTG. This reduction in DTG-induced dystonia by BMY 14802 may result its direct inhibitory effects against DTG at the sites, because BMY 14802 possesses potent sigma affinty. These findings imply that sigma ligands may be divided into two categories, dystonia-reinforcing and -reducing groups. Application of this theory should lead to the elucidation of the mechanism of neuroleptics-induced dystonia and other motor side effects.
Keywords
sigma sites
dystonia
1, 3 -di-o-tolylguanidine (DTG)
BMY 14802
neuroleptics
Note
原著
Published Date
1991-08
Publication Title
岡山医学会雑誌
Publication Title Alternative
Journal of Okayama Medical Association
Volume
volume103
Issue
issue7-8
Publisher
岡山医学会
Publisher Alternative
Okayama Medical Association
Start Page
749
End Page
757
ISSN
0030-1558
NCID
AN00032489
Content Type
Journal Article
Official Url
https://www.jstage.jst.go.jp/article/joma1947/103/7-8/103_7-8_749/_article/-char/ja/
Related Url
http://www.okayama-u.ac.jp/user/oma/index.html
language
日本語
Copyright Holders
岡山医学会
File Version
publisher
Refereed
True
Eprints Journal Name
joma