The role of dopamine D3 receptors in the mechanism of action of cariprazine

CNS Spectr. 2020 Jun;25(3):343-351. doi: 10.1017/S109285291900083X. Epub 2019 Apr 23.


Cariprazine is a new atypical antipsychotic drug (APD) with a unique pharmacodynamic profile, different from both typical and atypical APDs. Specifically, cariprazine acts as a partial agonist at the dopamine (DA) D2 and D3 receptors and serotonin 5-HT1A receptors, and as an antagonist at the 5-HT2B receptors. Moreover, it shows moderate affinities for adrenergic, histaminergic, and cholinergic receptors that are involved in mediating the side effects characteristic of typical APDs. In this review, we discuss the contribution of DA D3 receptors (D3Rs) in the etiology and pathophysiology of schizophrenia and the potential benefits that may be associated with a more selective targeting of D3R by APDs, as compared to other dopaminergic and non-dopaminergic receptor subtypes. Cariprazine, by acting on D3Rs, ameliorates anhedonia and cognitive deficits in animal models based on environmental or pharmacological manipulation. The reviewed results support the potential benefits of cariprazine in treating negative symptoms and cognitive deficits of schizophrenia, and therefore representing a promising approach in addressing the unmet clinical needs for the improved treatment of this serious neuropsychiatric disorder.

Keywords: Dopamine D3 receptors; antipsychotic drugs; cariprazine; cognitive deficits; negative symptoms; schizophrenia.

Publication types

  • Review

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Antipsychotic Agents / therapeutic use
  • Dopamine Agonists / pharmacology*
  • Dopamine Agonists / therapeutic use
  • Humans
  • Piperazines / pharmacology*
  • Piperazines / therapeutic use
  • Receptors, Dopamine D3 / agonists*
  • Receptors, Dopamine D3 / metabolism
  • Schizophrenia / drug therapy*


  • Antipsychotic Agents
  • Dopamine Agonists
  • Piperazines
  • Receptors, Dopamine D3
  • cariprazine