title: The discovery of potent and selective dopamine D4 receptor antagonists.
abstract: The identification of a novel dopamine receptor subtype, referred to as the D4 receptor, which binds the atypical antipsychotic drug clozapine with high potency, has led to the initiation of a drug discovery program that aims to find novel inhibitors of this receptor subtype. A selective screening strategy was utilized, in which 4500 compounds chosen on the basis of structural similarities to known biogenic amine receptor antagonists were tested against both the D4 and D2 dopamine receptor subtypes. A potent D4-selective compound was discovered.
authors.affiliation: Central Research Division, Pfizer Central Research, Groton, CT 06340, USA.
authors.forename: W S
authors.initials: WS
authors.lastname: Faraci
authors.forename: S H
authors.initials: SH
authors.lastname: Zorn
authors.forename: M A
authors.initials: MA
authors.lastname: Sanner
authors.forename: A
authors.initials: A
authors.lastname: Fliri
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D003024:Clozapine / Q000627:therapeutic use; D018492:Dopamine Antagonists / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D065127:Dopamine D2 Receptor Antagonists; D004353:Drug Evaluation, Preclinical; D006801:Humans; D050638:Receptors, Dopamine D4
chemical_list: D014150:Antipsychotic Agents; C493599:DRD4 protein, human; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D050638:Receptors, Dopamine D4; D003024:Clozapine