Selective dopamine D3 receptor antagonists: a review 2001-2005.
A growing body of evidence indicates that dopamine (DA) D(3) receptors are significantly involved in the control of drug-seeking behavior, and may play an important role in the pathophysiology of impulse control disorders and schizophrenia. This hypothesis has been difficult to test due to the lack of compounds with high selectivity for central DA D(3) receptors. Recently, however, the synthesis and characterization of new highly potent and selective DA D(3) receptor antagonists has permitted to characterize the role of the DA D(3) receptor in a wide range of preclinical animal models. Although the proof of efficacy of pharmacotherapeutic agents is to be derived ultimately from clinical trials, the preclinical findings that selective antagonism at DA D(3) receptors reduces the reinforcing efficacy of drugs of abuse, reverses cognitive deficits, and shows efficacy in animal models of schizophrenia add to an accumulating body of evidence that selective DA D(3) receptor antagonists may hold highest promise in the treatment of several neuropsychiatric diseases. The present review is aiming at describing current areas of interest and the possible future development of selective DA D(3) receptor antagonists by outlining about 40 patents and 100 publications in this research field between 2001 and 2005.
Micheli
Fabrizio
F
Department of Medicinal Chemistry, Glaxo SmithKline S.p.A., Via A. Fleming 4, 37135 Verona, Italy.
Heidbreder
Christian
C
D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy; D020650:Combinatorial Chemistry Techniques; D018492:Dopamine Antagonists / Q000737:chemistry / Q000145:classification / Q000627:therapeutic use*; D006801:Humans; D006860:Hydrogen Bonding; D007175:Impulsive Behavior / Q000235:genetics; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy; D013329:Structure-Activity Relationship; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000209:etiology
D018492:Dopamine Antagonists; D050637:Receptors, Dopamine D3