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

Elliott Richelson, Terry Souder

Research output: Contribution to journalArticlepeer-review

549 Scopus citations


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 (α1-adrenergic, α2-adrenergic, dopamine D2, histamine H1, 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 D2 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 H1 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. (C) 2000 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)29-39
Number of pages11
JournalLife Sciences
Issue number1
StatePublished - Nov 24 2000


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

ASJC Scopus subject areas

  • General Pharmacology, Toxicology and Pharmaceutics
  • General Biochemistry, Genetics and Molecular Biology


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