Cariprazine (RGH-188), a D^sub 3^-preferring dopamine D^sub 3^/D^sub 2^ receptor partial agonist antipsychotic candidate demonstrates anti-abuse potential in rats

• Published in: Psychopharmacology Vol. 226; no. 2; p. 285
• Main Authors: Román, V, Gyertyán, I, Sághy, K, Kiss, B, Szombathelyi, Zs
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer Nature B.V 01.03.2013
• Subjects: Dopamine; Drug abuse; Drug therapy; Psychotropic drugs
• DOI: 10.1007/s00213-012-2906-7
• ISSN: 0033-3158

Cariprazine (RGH-188) is a D^sub 3^-preferring dopamine D^sub 3^/D^sub 2^ 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 D^sub 2^ and D^sub 3^ 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 [ED^sub 50^] 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.[PUBLICATION ABSTRACT]