Schizophrenia and L-745,870, a novel dopamine D4 receptor antagonist.
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.
Bristow
L J
LJ
Department of Pharmacology, Merck, Sharp and Dohme, Neuroscience Research Centre, Terlings Park, Harlow, UK.
Kramer
M S
MS
Kulagowski
J
J
Patel
S
S
Ragan
C I
CI
Seabrook
G R
GR
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
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