title: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds.
abstract: Using radioligand binding assays and post-mortem normal human brain tissue, we obtained equilibrium dissociation constants (K(d)s) 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 (alpha1-adrenergic, alpha2-adrenergic, dopamine D2, histamine H1, muscarinic, and serotonin 5-HT1A, 5-HT1D, 5-HT2A, and 5-HT2C receptors). Iloperidone was the most potent drug at the two adrenergic receptors. ORG 5222 was the most potent drug at dopamine D2 and 5-HT2c receptors, while ziprasidone was the most potent compound at three serotonergic receptors (5-HT1A, 5-HT1D, and 5-HT2A). At the remaining two receptors, olanzapine was the most potent drug at the histamine H1 receptor (Kd=0.087 nM); clozapine at the muscarinic receptor (Kd=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.
authors.affiliation: Department of Psychiatry and Psychology, and Pharmacology, Mayo Foundation for Medical Education and Research and Mayo Clinic, Jacksonville, FL 32224, USA. richel@mayo.edu
authors.forename: E
authors.initials: E
authors.lastname: Richelson
authors.forename: T
authors.initials: T
authors.lastname: Souder
mesh_terms: D014150:Antipsychotic Agents / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D006801:Humans; D011869:Radioligand Assay; D011955:Receptors, Drug / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter