Schizophrenia and L-745,870, a novel dopamine D4 receptor antagonist

L J Bristow; M S Kramer; J Kulagowski; S Patel; C I Ragan; G R Seabrook

doi:10.1016/s0165-6147(97)01066-3

Schizophrenia and L-745,870, a novel dopamine D4 receptor antagonist

Trends Pharmacol Sci. 1997 Jun;18(6):186-8. doi: 10.1016/s0165-6147(97)01066-3.

Authors

L J Bristow¹, M S Kramer, J Kulagowski, S Patel, C I Ragan, G R Seabrook

Affiliation

¹ Department of Pharmacology, Merck, Sharp and Dohme, Neuroscience Research Centre, Terlings Park, Harlow, UK.

PMID: 9226994
DOI: 10.1016/s0165-6147(97)01066-3

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.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antipsychotic Agents / pharmacokinetics
Antipsychotic Agents / pharmacology
Antipsychotic Agents / therapeutic use*
Biological Availability
Clinical Trials as Topic
Dopamine Antagonists / pharmacokinetics
Dopamine Antagonists / pharmacology
Dopamine Antagonists / therapeutic use*
Dopamine D2 Receptor Antagonists*
Humans
Pyridines / pharmacokinetics
Pyridines / pharmacology
Pyridines / therapeutic use*
Pyrroles / pharmacokinetics
Pyrroles / pharmacology
Pyrroles / therapeutic use*
Receptors, Dopamine D4
Rodentia
Schizophrenia / drug therapy*
Schizophrenia / physiopathology

Substances

3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridine
Antipsychotic Agents
DRD4 protein, human
Dopamine Antagonists
Dopamine D2 Receptor Antagonists
Pyridines
Pyrroles
Receptors, Dopamine D4