RATIONALE: 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. OBJECTIVES: 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.
RATIONALE: 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 humancocaine addiction. OBJECTIVES: 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: Pradeep J Nathan; Barry V O'Neill; Karin Mogg; Brendan P Bradley; John Beaver; Massimo Bani; Emilio Merlo-Pich; Paul C Fletcher; Bridget Swirski; Annelize Koch; Chris M Dodds; Edward T Bullmore Journal: Int J Neuropsychopharmacol Date: 2011-07-12 Impact factor: 5.176
Authors: Thomas P Beresford; Lori Clapp; Brandon Martin; John L Wiberg; Julie Alfers; Henry F Beresford Journal: J Clin Psychopharmacol Date: 2005-08 Impact factor: 3.153
Authors: Andrew B Norman; Mantana K Norman; Michael R Tabet; Vladimir L Tsibulsky; Amadeo J Pesce Journal: Synapse Date: 2010-10-08 Impact factor: 2.562
Authors: Kenneth J Thiel; Jennifer M Wenzel; Nathan S Pentkowski; Rebecca J Hobbs; Andrea T Alleweireldt; Janet L Neisewander Journal: Behav Brain Res Date: 2010-06-19 Impact factor: 3.332
Authors: Karen D Ersche; Edward T Bullmore; Kevin J Craig; Shaila S Shabbir; Sanja Abbott; Ulrich Müller; Cinly Ooi; John Suckling; Anna Barnes; Barbara J Sahakian; Emilio V Merlo-Pich; Trevor W Robbins Journal: Arch Gen Psychiatry Date: 2010-06
Authors: Patrick D Worhunsky; Gustavo A Angarita; Zu Wei Zhai; David Matuskey; Jean-Dominique Gallezot; Robert T Malison; Richard E Carson; Marc N Potenza Journal: Neuropsychopharmacology Date: 2020-10-02 Impact factor: 7.853