Progress in developing D3 dopamine receptor ligands as potential therapeutic agents for neurological and neuropsychiatric disorders.
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, Parkinson's 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.
Luedtkea
Robert R
RR
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA. rluedtke@hsc.unt.edu
Mach
Robert H
RH
D000595:Amino Acid Sequence; D000818:Animals; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001665:Binding Sites; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D050637:Receptors, Dopamine D3; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology; D019966:Substance-Related Disorders / Q000188:drug therapy* / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
D001549:Benzamides; C493593:DRD3 protein, human; D008024:Ligands; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes