Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds.

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摘要：

Using radioligand binding assays and post-mortem normal human brain tissue, we obtained equilibrium dissociation constants (K ds) for nine new antipsychotic drugs (iloperidone, melperone, olanzapine, ORG 5222, quetiapine, risperidone, sertindole, ziprasidone, and zotepine), one metabolite of a new drug (9-OH-risperidone), and three older antipsychotics (clozapine, haloperidol, and pimozide) at nine different receptors (α 1-adrenergic, α 2-adrenergic, dopamine D 2, histamine H 1, muscarinic, and serotonin 5-HT 1A, 5-HT 1D, 5-HT 2A, and 5-HT 2C receptors). Iloperidone was the most potent drug at the two adrenergic receptors. ORG 5222 was the most potent drug at dopamine D 2 and 5-HT 2c receptors, while ziprasidone was the most potent compound at three serotonergic receptors (5-HT 1A, 5-HT 1D, and 5-HT 2A). At the remaining two receptors, olanzapine was the most potent drug at the histamine H 1 receptor (K d=0.087 nM); clozapine at the muscarinic receptor (K d=9 nM). Certain therapeutic and adverse effects, as well as certain drug interactions can be predicted from a drug's potency for blocking a specific receptor. These data can provide guidelines for the clinician in the choice of antipsychotic drug.

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关键词：

Histamine H 1 receptor Muscarinic receptor α 1-Adrenoceptor α 2-Adrenoceptor Dopamine D 2 receptor Serotonin 5-HT 1A receptor Serotonin 5-HT 2A receptor

DOI：

10.1016/S0024-3205(00)00911-5

被引量：

1166

年份：

2000