Inverse agonist properties of antipsychotic agents at cloned, human (h) serotonin (5-HT)1B and h5-HT1D receptors

被引：37

作者：

Audinot, V ^{[1
]}

Newman-Tancredi, A ^{[1
]}

Cussac, D ^{[1
]}

Millan, MJ ^{[1
]}

机构：

[1] Inst Rech Servier, Dept Psychopharmacol, Dept Mol & Cellular Pharmacol, F-78290 Croissy Sur Seine, Paris, France

来源：

NEUROPSYCHOPHARMACOLOGY | 2001年 / 25卷 / 03期

关键词：

5-HT1B; 5-HT1D; schizophrenia; 5-5-schizophrenia; antipsychotic; clozapine; inverse agonist;

D O I：

10.1016/S0893-133X(01)00237-8

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The actions of diverse antipsychotics at cloned h5-HT1B and h5-HT1D receptors were examined employing [H-3]-GR125,743 and [S-35]-GTP gammaS for determination of affinities and efficacies, respectively. Compared with hD(2) receptors, haloperidol, chlorpromazine and olanzapine showed markedly (> 100-fold) lower affinity for h5-HT1D and h5-HT1B receptors at which they expressed inverse agonist properties. Clozapine, risperidone and ocaperidone likewise behaved as inverse agonists at h5-HT1B and h5-HT1D receptors but their affinities were only similar to 10-fold lower than at hD2 receptors. Moreover, ziprasidone, S16924 and ORG5222 interacted at h5-HT1B and h5-HT1D receptors with affinities similar to hD(2) sites. While S16924 and ORG5222 were inverse agonists at h5-HT1B anti h5-HT1D sites, ziprasidone was an inverse agonist at h5-HT1D receptors yet a partial agonist tit h5-HT1B receptors. These actions of antipsychotics were abolished by the selective, neutral antagonist, S18127. In conclusion, with the exception cf ziprasidone, till antipsychotics were inverse agonists at h5-HT1B; and h5-HT1D receptors, although they differed markedly in their potency tit these sites as compared to hD(2) receptors. (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.

引用

页码：410 / 422

页数：13

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