title: Cariprazine (RGH-188), a D₃-preferring dopamine D₃/D₂ receptor partial agonist antipsychotic candidate demonstrates anti-abuse potential in rats.
abstract: BACKGROUND
  Cariprazine (RGH-188) is a D₃-preferring dopamine D₃/D₂ receptor partial agonist antipsychotic candidate for the treatment of schizophrenia and bipolar mania. Substance abuse is a frequent comorbidity of both disorders and is associated with serious health issues. Based on preclinical efficacy, dopamine D₂ and D₃ receptor partial agonists and antagonists are assumed to have relapse-preventing potential in human cocaine addiction.
  
  
  OBJECTIVE
  We investigated the anti-abuse potential of cariprazine in cocaine self-administration paradigms. Aripiprazole and bifeprunox were used as comparators because of their pharmacological similarity to cariprazine.
  
  
  METHODS
  The effects of compounds on cocaine's rewarding effect were investigated in a continuous self-administration regimen. The relapse-preventing potential of drugs was studied in rats with a history of cocaine self-administration after a period of complete abstinence in a relapse to cocaine-seeking paradigm.
  
  
  RESULTS
  Cariprazine, as well as aripiprazole and bifeprunox, were able to reduce the rewarding effect of cocaine (minimum effective doses were 0.17, 1, and 0.1 mg/kg, respectively) and attenuated relapse to cocaine seeking with half maximal effective dose [ED₅₀] values of 0.2, 4.2, and 0.17 mg/kg, respectively.
  
  
  CONCLUSIONS
  These results may predict a relapse-preventing action for cariprazine in humans in addition to its already established antipsychotic and antimanic efficacy.
authors.affiliation: Pharmacology and Drug Safety Research, Gedeon Richter Plc, Budapest, Hungary. v.roman@richter.hu
authors.forename: V
authors.initials: V
authors.lastname: Román
authors.forename: I
authors.initials: I
authors.lastname: Gyertyán
authors.forename: K
authors.initials: K
authors.lastname: Sághy
authors.forename: B
authors.initials: B
authors.lastname: Kiss
authors.forename: Zs
authors.initials: Z
authors.lastname: Szombathelyi
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole; D001583:Benzoxazoles / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D017448:Receptors, Dopamine D2 / Q000819:agonists; D055502:Secondary Prevention; D019966:Substance-Related Disorders / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents; D001583:Benzoxazoles; D018491:Dopamine Agonists; D010879:Piperazines; D015363:Quinolones; D017448:Receptors, Dopamine D2; D000068180:Aripiprazole; C509981:bifeprunox; C533287:cariprazine; D006220:Haloperidol