Progress in Developing D3 Dopamine Receptor Ligands as Potential Therapeutic Agents for Neurological and Neuropsychiatric Disorders

• Published in: Current pharmaceutical design Vol. 9; no. 8; pp. 643 - 671
• Main Authors: Luedtke, Robert, Mach, Robert
• Format: Journal Article
• Language: English
• Published: United Arab Emirates Bentham Science Publishers Ltd 01.01.2003
• Subjects: Amino Acid Sequence; Animals; Benzamides - chemistry; Benzamides - pharmacology; Benzamides - therapeutic use; Binding Sites; Drug Design; Humans; Ligands; Molecular Sequence Data; Parkinson Disease - drug therapy; Parkinson Disease - metabolism; Receptors, Dopamine D2 - drug effects; Receptors, Dopamine D2 - metabolism; Receptors, Dopamine D2 - physiology; Receptors, Dopamine D3; Schizophrenia - drug therapy; Schizophrenia - metabolism; Second Messenger Systems - physiology; Substance-Related Disorders - drug therapy; Substance-Related Disorders - metabolism; Tetrahydronaphthalenes - chemistry; Tetrahydronaphthalenes - pharmacology; Tetrahydronaphthalenes - therapeutic use
• ISSN: 1381-6128; 1873-4286
• DOI: 10.2174/1381612033391199

The dopamine D3 receptor has been the subject of a tremendous amount of research since its discovery in 1990. A previous review of this subject [3] described the advances in molecular biology and neuroanatomical localization of the D3 receptor, with a special emphasis on schizophrenia. In the current review, we attempt to describe recent advances in the biochemistry and pharmacology of the D3 receptor from the molecular to the behavioral level. Evidence linking an alteration in D3 receptor function as playing an important role in the etiology of a variety of CNS disorders, including schizophrenia, Parkinsons Disease, and substance abuse is also provided. Also discussed are the recent developments in attempting to map the ligand-binding domains of the D2 and D3 receptors. A. survey of the literature, including a description of the medicinal chemistry approaches toward developing D3-selective ligands, is also presented in this review.