title: Schizophrenia and L-745,870, a novel dopamine D4 receptor antagonist.
abstract: The discovery of a novel high-affinity and selective dopamine D4 receptor antagonist, L-745,870, and the results of clinical trials with this compound are reviewed. Despite several lines of evidence which suggest that a selective D4 receptor antagonist may be an effective antipsychotic agent with a lower propensity to induce extrapyramidal side-effects, L-745,870 was ineffective as an antipsychotic in humans.
authors.affiliation: Department of Pharmacology, Merck, Sharp and Dohme, Neuroscience Research Centre, Terlings Park, Harlow, UK.
authors.forename: L J
authors.initials: LJ
authors.lastname: Bristow
authors.forename: M S
authors.initials: MS
authors.lastname: Kramer
authors.forename: J
authors.initials: J
authors.lastname: Kulagowski
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.forename: C I
authors.initials: CI
authors.lastname: Ragan
authors.forename: G R
authors.initials: GR
authors.lastname: Seabrook
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001682:Biological Availability; D002986:Clinical Trials as Topic; D018492:Dopamine Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D065127:Dopamine D2 Receptor Antagonists; D006801:Humans; D011725:Pyridines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011758:Pyrroles / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D050638:Receptors, Dopamine D4; D012377:Rodentia; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: C099630:3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridine; D014150:Antipsychotic Agents; C493599:DRD4 protein, human; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D011725:Pyridines; D011758:Pyrroles; D050638:Receptors, Dopamine D4