Cariprazine (RGH-188), a D₃-preferring dopamine D₃/D₂ receptor partial agonist antipsychotic candidate demonstrates...

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.

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.

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.

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.

These results may predict a relapse-preventing action for cariprazine in humans in addition to its already established antipsychotic and antimanic efficacy.