New Pharmacological Targets for the Treatment of Schizophrenia: A Lit-erature Review

被引：24

作者：

Ventriglio, Antonio ^{[1
]}

Bellomo, Antonello ^{[1
]}

Ricci, Fabiana ^{[1
]}

Magnifico, Giuseppe ^{[1
]}

Rinaldi, Angelo ^{[1
]}

Borraccino, Luisa ^{[1
]}

Piccininni, Carla ^{[1
]}

Cuoco, Federica ^{[1
]}

Gianfelice, Giulia ^{[2
]}

Fornaro, Michele ^{[3
]}

Delle Monache, Sonia ^{[4
]}

De Berardis, Domenico ^{[2
]}

机构：

[1] Univ Foggia, Dept Clin & Expt Med, Foggia, Italy

[2] ASL Teramo, Dept Mental Hlth, Teramo, Italy

[3] Sch Med Federico II Naples, Dept Neurosci Reprod Sci & Odontostomatol, Naples, Italy

[4] Hosp G Mazzini, Cardiothorac Vasc Dept, ASL 4, Teramo, Italy

来源：

CURRENT TOPICS IN MEDICINAL CHEMISTRY | 2021年 / 21卷 / 16期

关键词：

First episode of psychosis; Schizophrenia; Glutamate; Cannabidiol; Adjunctive antipsychotic therapies; COX-2; in-hibitors; POSITIVE ALLOSTERIC MODULATORS; PLACEBO-CONTROLLED TRIAL; RANDOMIZED DOUBLE-BLIND; ADD-ON THERAPY; NEGATIVE SYMPTOMS; COGNITIVE ENHANCEMENT; ADJUNCTIVE TREATMENT; POSSIBLE INVOLVEMENT; PSYCHOTIC SYMPTOMS; GLUTAMATE SYSTEM;

D O I：

10.2174/1568026621666210701103147

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Background: The pharmacological treatment of schizophrenia is currently based on the employment of antipsychotic medications showing an antagonism of dopaminergic and serotoninergic inhibitors. 20-40% of patients are drug-resistant or residually symptomatic in the long-term antipsychotic treatment, and new strategies are needed for improving their functional and cognitive impairment. Methods: This systematic review has summarized evidences from the literature regarding the newer pharmacological targets proposed for the treatment of psychosis. We included 128 peer -reviewed articles and 5 other relevant sources published from 2002 to 2020 on PubMed EMBASE, The Cochrane Library, and Google Scholar. Results: The possible role of glutamate and its receptors as targets of the antipsychotic mechanism of action has been described. Glutamatergic neurotransmission and NMDA receptors hypofunction are involved in the neurobiological explanatory model of psychosis and possibly targeted for the successful treatment of cognitive and residual symptoms. Results show an efficacy of D-cycloserine (antagonist at the Glycine site of the NMDA-R) in the treatment of negative symptoms of schizophrenia as well as Memantine (NMDA-Receptor antagonist) for cognition and psychopathology. The putative antipsychotic effect of cannabidiol on positive symptoms and cognition will also be discussed. The action on serotoninergic and GABAergic receptors will be considered as a new pharmacological target, with a possible efficacy of Vabicaserin on symptoms of psychosis. Mynocicline has shown to induce improvements in cognitive symptoms in schizophrenia, as well as Erythropoietin. Oxytocin has been reported to have an antipsychotic-like effect; moreover, COX-2 inhibitors lead to a reduction in positive symptoms of psychosis, specifically in the first episode of illness. Conclusion: This narrative report suggests a promising role of new agents in the treatment of Schizophrenia; however, more research is needed to approve their clinical employment.

引用

页码：1500 / 1516

页数：17

共 140 条

[1] Discovery of N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide as an agonist of the α7 nicotinic acetylcholine receptor:: In vitro and in vivo activity [J].

Acker, Brad A. ;

Jacobsen, E. Jon ;

Rogers, Bruce N. ;

Wishka, Donn G. ;

Reitz, Steven C. ;

Piotrowski, David W. ;

Myers, Jason K. ;

Wolfe, Mark L. ;

Groppi, Vincent E. ;

Thornburgh, Bruce A. ;

Tinholt, Paula M. ;

Walters, Rodney R. ;

Olson, Barbara A. ;

Fitzgerald, Laura ;

Staton, Brian A. ;

Raub, Thomas J. ;

Krause, Michael ;

Li, Kai S. ;

Hoffmann, William E. ;

Hajos, Mihaly ;

Hurst, Raymond S. ;

Walker, Daniel P. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (12) :3611-3615

[2] Celecoxib as adjunctive therapy in schizophrenia: A double-blind, randomized and placebo-controlled trial [J].

Akhondzadeh, Shahin ;

Tabatabaee, Maryam ;

Amini, Homayoun ;

Abhari, Seyed Ali Ahmadi ;

Abbasi, Seyed Hesamedin ;

Behnam, Behnaz .

SCHIZOPHRENIA RESEARCH, 2007, 90 (1-3) :179-185

[3]

Amiaz R, 2015, ISR J PSYCHIATR REL, V52, P12

[4]

[Anonymous], 2009, CARDIOVASC PSYCHIAT

[5]

Arabzadeh Somaye, 2018, Iran J Psychiatry, V13, P1

[6]

Arnold JC, 2012, CURR PHARM DESIGN, V18, P5113, DOI 10.2174/138161212802884726

[7] Emotion recognition and oxytocin in patients with schizophrenia [J].

Averbeck, B. B. ;

Bobin, T. ;

Evans, S. ;

Shergill, S. S. .

PSYCHOLOGICAL MEDICINE, 2012, 42 (02) :259-266

[8] Opposite Effects of Δ-9-Tetrahydrocannabinol and Cannabidiol on Human Brain Function and Psychopathology [J].

Bhattacharyya, Sagnik ;

Morrison, Paul D. ;

Fusar-Poli, Paolo ;

Martin-Santos, Rocio ;

Borgwardt, Stefan ;

Winton-Brown, Toby ;

Nosarti, Chiara ;

O'Carroll, Colin M. ;

Seal, Marc ;

Allen, Paul ;

Mehta, Mitul A. ;

Stone, James M. ;

Tunstall, Nigel ;

Giampietro, Vincent ;

Kapur, Shitij ;

Murray, Robin M. ;

Zuardi, Antonio W. ;

Crippa, Jose A. ;

Atakan, Zerrin ;

McGuire, Philip K. .

NEUROPSYCHOPHARMACOLOGY, 2010, 35 (03) :764-774

[9] Group II Metabotropic Glutamate Receptors Mediate Presynaptic Inhibition of Excitatory Transmission in Pyramidal Neurons of the Human Cerebral Cortex [J].

Bocchio, Marco ;

Lukacs, Istvan P. ;

Stacey, Richard ;

Plaha, Puneet ;

Apostolopoulos, Vasileios ;

Livermore, Laurent ;

Sen, Arjune ;

Ansorge, Olaf ;

Gillies, Martin J. ;

Somogyi, Peter ;

Capogna, Marco .

FRONTIERS IN CELLULAR NEUROSCIENCE, 2019, 12

[10] The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial [J].

Boggs, Douglas L. ;

Surti, Toral ;

Gupta, Aarti ;

Gupta, Swapnil ;

Niciu, Mark ;

Pittman, Brian ;

Martin, Ashley M. Schnakenberg ;

Thurnauer, Halle ;

Davies, Andrew ;

D'Souza, Deepak C. ;

Ranganathan, Mohini .

PSYCHOPHARMACOLOGY, 2018, 235 (07) :1923-1932

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