title: Dopamine D3 receptor antagonists: a patent review (2007 - 2012).
abstract: BACKGROUND
  The synthesis and characterization of new highly potent and selective dopamine (DA) D3 receptor antagonists has permitted to characterize the role of the DA D3 receptor in the control of drug-seeking behavior and in the pathophysiology of impulse control disorders and schizophrenia.
  
  
  METHODS
  In the present review, the authors will first describe most recent classes of DA D3 receptor antagonists by reviewing about 43 patent applications during the 2007 - 2012 period; they will then outline the biological rationale in support of the use of selective DA D3 receptor antagonists in the treatment of drug addiction, impulse control disorders and schizophrenia.
  
  
  CONCLUSIONS
  The strongest clinical application and potential for selective DA D3 receptor antagonists lies in the reduction of drug-induced incentive motivation, the attenuation of drug's rewarding efficacy and the reduction in reinstatement of drug-seeking behavior triggered either by re-exposure to the drug itself, re-exposure to environmental cues that had been previously associated with drug-taking behavior or stress. The selectivity of these antagonists together with reduced lipophilicity (minimizing unspecific binding), increased brain penetration and improved physico-chemical profile are all key factors for clinical efficacy and safety.
authors.affiliation: Drug Design & Discovery, Aptuit Verona srl, Via A Fleming 4, 37135 Verona, Italy. Fabrizio.Micheli@aptuit.com
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Micheli
authors.forename: Christian
authors.initials: C
authors.lastname: Heidbreder
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D002986:Clinical Trials as Topic; D003071:Cognition / Q000187:drug effects; D003463:Cues; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000188:drug therapy / Q000523:psychology; D018492:Dopamine Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D004542:Ejaculation / Q000187:drug effects; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000517:prevention & control; D008032:Limbic System / Q000187:drug effects / Q000502:physiology; D008297:Male; D009042:Motivation / Q000187:drug effects; D010330:Patents as Topic; D016032:Randomized Controlled Trials as Topic; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors*; D012201:Reward; D012559:Schizophrenia / Q000188:drug therapy; D055502:Secondary Prevention; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000523:psychology
chemical_list: D000978:Antiparkinson Agents; D018492:Dopamine Antagonists; D050637:Receptors, Dopamine D3