Experimental Serotonergic Agents for the Treatment of Schizophrenia

Enrico Capuzzi,1 Alice Caldiroli,1 Veronica Ciscato,2 Stefania Russo,2 Massimiliano Buoli3,4 1Psychiatric Department, Azienda Socio Sanitaria Territoriale Monza, Monza, Italy; 2Department of Medicine and Surgery, University of Milano Bicocca, Monza, MB, 20900, Italy; 3Department of Neurosciences and...

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Main Authors: Capuzzi E, Caldiroli A, Ciscato V, Russo S, Buoli M
Format: Article
Language:English
Published: Dove Medical Press 2021-02-01
Series:Journal of Experimental Pharmacology
Subjects:
Online Access:https://www.dovepress.com/experimental-serotonergic-agents-for-the-treatment-of-schizophrenia-peer-reviewed-fulltext-article-JEP
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author Capuzzi E
Caldiroli A
Ciscato V
Russo S
Buoli M
author_facet Capuzzi E
Caldiroli A
Ciscato V
Russo S
Buoli M
author_sort Capuzzi E
collection DOAJ
description Enrico Capuzzi,1 Alice Caldiroli,1 Veronica Ciscato,2 Stefania Russo,2 Massimiliano Buoli3,4 1Psychiatric Department, Azienda Socio Sanitaria Territoriale Monza, Monza, Italy; 2Department of Medicine and Surgery, University of Milano Bicocca, Monza, MB, 20900, Italy; 3Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico, Milan, 20122, Italy; 4Department of Pathophysiology and Transplantation, University of Milan, Milan, ItalyCorrespondence: Massimiliano BuoliDepartment of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan, 20122, ItalyTel +39-02-55035983Fax +39-02-55035952Email massimiliano.buoli@unimi.itAbstract: Schizophrenia remains one of the most chronic and highly disabling mental disorder. To date, the pathomechanism of schizophrenia is not fully understood and current treatments are characterized by some limitations. First- and second-generation antipsychotics have shown clinical efficacy in treating positive symptoms, while are poorly effective on both negative symptoms and cognitive deficits. Moreover, they can involve many metabolic and neurological side effects, leading to low therapeutic compliance. Many evidence suggested that serotonin may play a complex role in the neurobiology of schizophrenia. Therefore, new drugs targeting 5-HT receptors (5-HTRs) have become an important area of research in schizophrenia in the hope that treatment efficacy may be improved without inducing side effects observed with currently available antipsychotics. Research using the main database sources was conducted to obtain an overview of preclinical and clinical pharmacological 5-HTR-targeted therapies in patients with schizophrenia. We identified 17 experimental serotonergic agents, under study for their potential use in schizophrenia treatment. Particularly, AVN-211, LuAF-35700 and Brilaroxazine are currently under clinical development. Moreover, some compounds showed some pro-cognitive and antipsychotic-like properties in animal models, while other agents showed contradictory effects in improving symptoms and were removed from the development program. Although some serotonergic drugs seem promising for improving the treatment of schizophrenia, further studies regarding the pathophysiological mechanisms of schizophrenia and novel compounds as well as high-quality trials are necessary in order to improve schizophrenia outcomes.Keywords: schizophrenia, serotonin, experimental agents, negative symptoms, cognitive deficits
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spelling doaj.art-f6ebf0316ded46dea6237343f188b75e2022-12-21T18:25:43ZengDove Medical PressJournal of Experimental Pharmacology1179-14542021-02-01Volume 13496761781Experimental Serotonergic Agents for the Treatment of SchizophreniaCapuzzi ECaldiroli ACiscato VRusso SBuoli MEnrico Capuzzi,1 Alice Caldiroli,1 Veronica Ciscato,2 Stefania Russo,2 Massimiliano Buoli3,4 1Psychiatric Department, Azienda Socio Sanitaria Territoriale Monza, Monza, Italy; 2Department of Medicine and Surgery, University of Milano Bicocca, Monza, MB, 20900, Italy; 3Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico, Milan, 20122, Italy; 4Department of Pathophysiology and Transplantation, University of Milan, Milan, ItalyCorrespondence: Massimiliano BuoliDepartment of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan, 20122, ItalyTel +39-02-55035983Fax +39-02-55035952Email massimiliano.buoli@unimi.itAbstract: Schizophrenia remains one of the most chronic and highly disabling mental disorder. To date, the pathomechanism of schizophrenia is not fully understood and current treatments are characterized by some limitations. First- and second-generation antipsychotics have shown clinical efficacy in treating positive symptoms, while are poorly effective on both negative symptoms and cognitive deficits. Moreover, they can involve many metabolic and neurological side effects, leading to low therapeutic compliance. Many evidence suggested that serotonin may play a complex role in the neurobiology of schizophrenia. Therefore, new drugs targeting 5-HT receptors (5-HTRs) have become an important area of research in schizophrenia in the hope that treatment efficacy may be improved without inducing side effects observed with currently available antipsychotics. Research using the main database sources was conducted to obtain an overview of preclinical and clinical pharmacological 5-HTR-targeted therapies in patients with schizophrenia. We identified 17 experimental serotonergic agents, under study for their potential use in schizophrenia treatment. Particularly, AVN-211, LuAF-35700 and Brilaroxazine are currently under clinical development. Moreover, some compounds showed some pro-cognitive and antipsychotic-like properties in animal models, while other agents showed contradictory effects in improving symptoms and were removed from the development program. Although some serotonergic drugs seem promising for improving the treatment of schizophrenia, further studies regarding the pathophysiological mechanisms of schizophrenia and novel compounds as well as high-quality trials are necessary in order to improve schizophrenia outcomes.Keywords: schizophrenia, serotonin, experimental agents, negative symptoms, cognitive deficitshttps://www.dovepress.com/experimental-serotonergic-agents-for-the-treatment-of-schizophrenia-peer-reviewed-fulltext-article-JEPschizophreniaserotoninexperimental agentsnegative symptomscognitive deficits
spellingShingle Capuzzi E
Caldiroli A
Ciscato V
Russo S
Buoli M
Experimental Serotonergic Agents for the Treatment of Schizophrenia
Journal of Experimental Pharmacology
schizophrenia
serotonin
experimental agents
negative symptoms
cognitive deficits
title Experimental Serotonergic Agents for the Treatment of Schizophrenia
title_full Experimental Serotonergic Agents for the Treatment of Schizophrenia
title_fullStr Experimental Serotonergic Agents for the Treatment of Schizophrenia
title_full_unstemmed Experimental Serotonergic Agents for the Treatment of Schizophrenia
title_short Experimental Serotonergic Agents for the Treatment of Schizophrenia
title_sort experimental serotonergic agents for the treatment of schizophrenia
topic schizophrenia
serotonin
experimental agents
negative symptoms
cognitive deficits
url https://www.dovepress.com/experimental-serotonergic-agents-for-the-treatment-of-schizophrenia-peer-reviewed-fulltext-article-JEP
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