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

Published online by Cambridge University Press:  23 April 2019

Francesca Calabrese ,
Frank I. Tarazi Open the ORCID record for Frank I. Tarazi [Opens in a new window] ,
Giorgio Racagni  and
Marco A. Riva Open the ORCID record for Marco A. Riva [Opens in a new window]
Francesca Calabrese
Affiliation:
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
Frank I. Tarazi
Affiliation:
Department of Psychiatry and Neuroscience Program, Harvard Medical School and McLean Hospital, Boston, MA, USA
Giorgio Racagni
Affiliation:
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy Associazione di Psicofarmacologia, Milan, Italy
Marco A. Riva*
Affiliation:
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
*
*Address correspondence to: Marco A. Riva, Professor, Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133Milan, Italy. (Email: [email protected])
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Abstract

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 receptorscariprazineantipsychotic drugsschizophrenianegative symptomscognitive deficits
Type
Review
Information
CNS Spectrums , Volume 25 , Issue 3 , June 2020 , pp. 343 - 351
Copyright
© Cambridge University Press 2019

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