Cited by 998Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorTreatment of Major Depression

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Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs

Miyamoto, S, Duncan, G E, Marx, C E, Lieberman, J A·2005·Molecular Psychiatry

DOI 10.1038/sj.mp.4001556

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Abstract

The treatment of schizophrenia has evolved over the past half century primarily in the context of antipsychotic drug development. Although there has been significant progress resulting in the availability and use of numerous medications, these reflect three basic classes of medications (conventional (typical), atypical and dopamine partial agonist antipsychotics) all of which, despite working by varying mechanisms of actions, act principally on dopamine systems. Many of the second-generation (atypical and dopamine partial agonist) antipsychotics are believed to offer advantages over first-generation agents in the treatment for schizophrenia. However, the pharmacological properties that confer the different therapeutic effects of the new generation of antipsychotic drugs have remained elusive, and certain side effects can still impact patient health and quality of life. Moreover, the efficacy of antipsychotic drugs is limited prompting the clinical use of adjunctive pharmacy to augment the effects of treatment. In addition, the search for novel and nondopaminergic antipsychotic drugs has not been successful to date, though numerous development strategies continue to be pursued, guided by various pathophysiologic hypotheses. This article provides a brief review and critique of the current therapeutic armamentarium for treating schizophrenia and drug development strategies and theories of mechanisms of action of antipsychotics, and focuses on novel targets for therapeutic agents for future drug development.

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BindingDB Entry 50031251: Discovery of 4-(5-methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane (CP-810,123), a novel alpha 7 nicotinic acetylcholine receptor agonist for the treatment of cognitive disorders in schizophrenia: synthesis, SAR development, and in vivo efficacy in cognition models.
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BindingDB (2020) · UC San Diego · doi:10.7270/q26h4md0
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BindingDB (2020) · UC San Diego · doi:10.7270/q218399k
BindingDB Entry 50047329: Synthesis and biological activities of indolizine derivatives as alpha-7 nAChR agonists.
BindingDB (2017) · UC San Diego · doi:10.7270/q2w37z6n
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BindingDB (2023) · UC San Diego · doi:10.7270/q25x2dsh
BindingDB Entry 50006753: 3-Amino-chromanes and Tetrahydroquinolines as Selective 5-HT
BindingDB (2021) · UC San Diego · doi:10.7270/q2df6vgq

Authors: Miyamoto, S., Duncan, G. E., Marx, C. E., & Lieberman, J. A.
Affiliations: St. Marianna University School of Medicine (JP)
University of North Carolina at Chapel Hill (US)
Duke Medical Center (US)
Corresponding author: Lieberman, J A
Venue: Molecular Psychiatry
Publisher: Springer Science and Business Media LLC
Published: 2004-08-03
Volume: 10
Issue: 1
Pages: 79-104
ISSN: 1359-4184 (ISSN-L)
1476-5578
DOI: 10.1038/sj.mp.4001556
OpenAlex: W2132980997
Cited by: 988
References: 393
Citations by year: 2026: 23 · 2025: 25 · 2024: 32 · 2023: 40 · 2022: 37 · 2021: 40 · 2020: 45 · 2019: 42 · 2018: 40 · 2017: 41 · 2016: 54 · 2015: 52 · 2014: 46 · 2013: 72 · 2012: 66
FWCI: 4.72
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Molecular Psychiatry (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Mental Health (MH064065, P50MH064065)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords: schizophrenia, antipsychotic drugs, dopamine D2 receptor, atypical antipsychotics, partial dopamine agonist, typical antipsychotics, mechanism of action, antipsychotic adverse effects, adjunctive pharmacotherapy, antipsychotic drug development, schizophrenia pathophysiology
MeSH terms: Behavioral Symptoms, Humans, Schizophrenia, Antipsychotic Agents, Drug Design, Dopamine Agents, Receptors, Dopamine D2, Receptors, Glutamate, Excitatory Amino Acid Agents

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Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs

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