Dopamine D3 receptor antagonists: a patent review (2007 - 2012).

INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.