Cited by 179Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

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Mechanisms of action of second generation antipsychotic drugs in schizophrenia: insights from brain imaging studies

Abi-Dargham, Anissa, Laruelle, Marc·2005·European Psychiatry

DOI 10.1016/j.eurpsy.2004.11.003

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Abstract

Multiple lines of evidence including recent imaging studies suggest that schizophrenia is associated with an imbalance of the dopaminergic system, entailing hyperstimulation of striatal dopamine (DA) D2 receptors and understimulation of cortical DA D1 receptors. This DA endophenotype presumably emerges from the background of a more general synaptic dysconnectivity, involving alterations in N-methyl-d-aspartate (NMDA) and glutamatergic (GLU) functions. Equally important is the fact that this DA dysregulation might further impair NMDA transmission. The first generation antipsychotic (FGA) drugs are characterized by high affinity to and generally high occupancy of D2 receptors. The efficacy of FGAs is limited by a high incidence of extrapyramidal side-effects (EPS). Second generation antipsychotic (SGA) drugs display reduced EPS liability and modest but clinically significant enhanced therapeutic efficacy. Compared to FGAs, the improved therapeutic action of SGAs probably derives from a more moderate D2 receptor blockade. We will review the effects of SGAs on other neurotransmitter systems and conclude by highlighting the importance of therapeutic strategies aimed at directly increasing prefrontal DA, D1 receptor transmission or NMDA transmission to enhance the therapeutic effect of moderate D2 receptor antagonism.

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Authors: Abi-Dargham, A., & Laruelle, M.
Affiliations: New York State Psychiatric Institute (US)
Venue: European Psychiatry
Publisher: Cambridge University Press (CUP)
Published: 2005-01
Volume: 20
Issue: 1
Pages: 15-27
ISSN: 0924-9338 (ISSN-L)
1778-3585
DOI: 10.1016/j.eurpsy.2004.11.003
OpenAlex: W2029915913
Cited by: 179
References: 175
Citations by year: 2026: 6 · 2025: 5 · 2024: 5 · 2023: 5 · 2022: 3 · 2021: 1 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 4 · 2016: 8 · 2015: 7 · 2014: 14 · 2013: 10 · 2012: 17
FWCI: 1.46
Type: journal article
Language: en
Open access: closed
Licence: www.cambridge.org/core/terms (unspecified, 5584 d)
Locations: European Psychiatry (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5k08mh001594-05, 5k02mh064178-03)
National Institute of Mental Health (K02 MH064178-01A2, K02MH01603-01, K02MH001603, K08 MH01594-01)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: atypical antipsychotics, schizophrenia, dopaminergic system, dopamine D2 receptor antagonism, dopamine D1 receptor, striatal dopamine, NMDA receptor, glutamatergic neurotransmission, extrapyramidal symptoms, typical antipsychotics, prefrontal dopamine, neuroimaging
MeSH terms: Brain, Dopamine, Humans, Schizophrenia, Antipsychotic Agents, Tomography, Emission-Computed, Single-Photon, N-Methylaspartate, Receptors, Dopamine D1, Glutamic Acid, Positron-Emission Tomography

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Mechanisms of action of second generation antipsychotic drugs in schizophrenia: insights from brain imaging studies

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