Effects of perospirone (SM-9018), a potential atypical neuroleptic, on dopamine D-1 receptor-mediated vacuous chewing movement in rats: A role of 5-HT2 receptor blocking activity

被引:11
作者
Ohno, Y
IshidaTokuda, K
Ishibashi, T
Nakamura, M
机构
[1] Research Center, Sumitomo Pharmaceuticals Co., Ltd., 3-1-98 Kasugade-naka, Konohana-ku
关键词
perospirone (SM-9018); haloperidol; neuroleptics; vacuous chewing movement; D-1; receptors; 5-HT2; tardive dyskinesia;
D O I
10.1016/S0091-3057(96)00468-6
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
We compared the acute and subacute effects of perospirone (SM-9018), a novel neuroleptic with potent 5-HT2 and D-2 blocking actions, and of haloperidol (HAL) on dopamine D-1 receptor-mediated vacuous chewing movement (VCM) in rats. A selective D-1 agonist, SKF 38393 (SKF), markedly increased the incidence of VCM, which was blocked by SCH 23390 (a D-1 antagonist) but not by sulpiride (a D-2 antagonist). Perospirone and HAL inhibited the SKF-induced VCM in a dose-dependent manner. The potency of the inhibitory actions of perospirone was considerably weaker (about 30 times) than that of HAL despite their similar affinities for D-1 receptors. Subacute treatment with perospirone for 2 weeks failed to affect the behavioral sensitivity of rats to SKF. However, the HAL treatment markedly enhanced the incidence of the SKF-induced VCM. On the other hand, the selective 5-HT2 antagonists ritanserin and ketanserin significantly reduced the inhibitory actions of HAL and SCH 23390 on the SKF-induced VCM. In addition, combined treatment of ritanserin with HAL for 2 weeks abolished the enhancement of SKF-induced VCM by HAL treatment. These findings suggest that perospirone is weaker than HAL in altering the behavioral sensitivity of D-1 receptor-mediated VCM under repeated administration, which may be related to the 5-HT2 blocking activity of perospirone. (C) 1997 Elsevier Science Inc.
引用
收藏
页码:889 / 895
页数:7
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