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Review

Dopamine, Cognitive Impairments and Second-Generation Antipsychotics: From Mechanistic Advances to More Personalized Treatments

1
Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
2
Genetics of Cognition laboratory, Neuroscience area, Istituto Italiano di Tecnologia, 16163 Genova, Italy
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2020, 13(11), 365; https://doi.org/10.3390/ph13110365
Received: 11 October 2020 / Revised: 31 October 2020 / Accepted: 3 November 2020 / Published: 5 November 2020
(This article belongs to the Special Issue Molecular and Cellular Targets of Old and New Atypical Antipsychotics)
The pharmacological treatment of cognitive impairments associated with schizophrenia is still a major unmet clinical need. Indeed, treatments with available antipsychotics generate highly variable cognitive responses among patients with schizophrenia. This has led to the general assumption that antipsychotics are ineffective on cognitive impairment, although personalized medicine and drug repurposing approaches might scale down this clinical issue. In this scenario, evidence suggests that cognitive improvement exerted by old and new atypical antipsychotics depends on dopaminergic mechanisms. Moreover, the newer antipsychotics brexpiprazole and cariprazine, which might have superior clinical efficacy on cognitive deficits over older antipsychotics, mainly target dopamine receptors. It is thus reasonable to assume that despite more than 50 years of elusive efforts to develop novel non-dopaminergic antipsychotics, dopamine receptors remain the most attractive and promising pharmacological targets in this field. In the present review, we discuss preclinical and clinical findings showing dopaminergic mechanisms as key players in the cognitive improvement induced by both atypical antipsychotics and potential antipsychotics. We also emphasize the concept that these mechanistic advances, which help to understand the heterogeneity of cognitive responses to antipsychotics, may properly guide treatment decisions and address the unmet medical need for the management of cognitive impairment associated with schizophrenia. View Full-Text
Keywords: cognition; schizophrenia; dopamine receptors; second-generation antipsychotics cognition; schizophrenia; dopamine receptors; second-generation antipsychotics
MDPI and ACS Style

Torrisi, S.A.; Laudani, S.; Contarini, G.; De Luca, A.; Geraci, F.; Managò, F.; Papaleo, F.; Salomone, S.; Drago, F.; Leggio, G.M. Dopamine, Cognitive Impairments and Second-Generation Antipsychotics: From Mechanistic Advances to More Personalized Treatments. Pharmaceuticals 2020, 13, 365. https://doi.org/10.3390/ph13110365

AMA Style

Torrisi SA, Laudani S, Contarini G, De Luca A, Geraci F, Managò F, Papaleo F, Salomone S, Drago F, Leggio GM. Dopamine, Cognitive Impairments and Second-Generation Antipsychotics: From Mechanistic Advances to More Personalized Treatments. Pharmaceuticals. 2020; 13(11):365. https://doi.org/10.3390/ph13110365

Chicago/Turabian Style

Torrisi, Sebastiano A., Samuele Laudani, Gabriella Contarini, Angelina De Luca, Federica Geraci, Francesca Managò, Francesco Papaleo, Salvatore Salomone, Filippo Drago, and Gian M. Leggio 2020. "Dopamine, Cognitive Impairments and Second-Generation Antipsychotics: From Mechanistic Advances to More Personalized Treatments" Pharmaceuticals 13, no. 11: 365. https://doi.org/10.3390/ph13110365

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