Dopamine D3 receptor antagonists as therapeutic agents

Dopamine D3 receptor antagonists could offer benefit in reducing cognitive and negative symptoms of schizophrenia without eliciting extrapyramidal symptoms; they could also reduce relapse to cocaine, heroin and other classes of abused drugs. The behavioral and pathophysiological role of the dopamine...

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Bibliographic Details
Published in:Drug discovery today 2005-07, Vol.10 (13), p.917-925
Main Authors: Joyce, Jeffrey N., Millan, Mark J.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
cocaine
cognition
Dopamine Antagonists - chemistry
Dopamine Antagonists - therapeutic use
extrapyramidal
General pharmacology
Humans
limbic system
Medical sciences
Molecular Structure
Nitriles - therapeutic use
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
positive symptoms
Receptors, Dopamine D3 - antagonists & inhibitors
Receptors, Dopamine D3 - physiology
Schizophrenia
Substance-Related Disorders - physiopathology
Substance-Related Disorders - prevention & control
Technology, Pharmaceutical - methods
Technology, Pharmaceutical - trends
Tetrahydroisoquinolines - therapeutic use
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Summary:Dopamine D3 receptor antagonists could offer benefit in reducing cognitive and negative symptoms of schizophrenia without eliciting extrapyramidal symptoms; they could also reduce relapse to cocaine, heroin and other classes of abused drugs. The behavioral and pathophysiological role of the dopamine D3 receptor, which was deduced from anatomical, lesion and drug treatment studies in the ten years following cloning of the receptor, indicated that its functions differed from those of the D2 receptor. There is increasingly strong evidence that D3 receptor antagonists will be effective antipsychotic agents. In this regard, an amelioration of the negative and cognitive symptoms of schizophrenia holds the most promise for D3 receptor antagonists, a concept currently under clinical evaluation. In addition, D3 receptors could be involved in behavioral sensitization and the potential application of D3 receptor antagonists in the treatment of drug abuse is undergoing intensive experimental investigation.
ISSN:1359-6446
1878-5832
DOI:10.1016/S1359-6446(05)03491-4