Understanding the Mechanism of Action of Atypical Antipsychotic Drugs: A Review of Compounds in Use and Development
Abstract
The thrust of development of new antipsychotic drugs has been to identify new compounds that have enhanced antipsychotic efficacy and have lesser side-effects than standard neuroleptic compounds. Drug development strategies no longer concentrate on D 2 receptor antagonism but aim to produce novel compounds. The following have been pursued: (a) selective dopamine receptor antagonists; (b) serotonin receptor agonists and antagonists (5-HT 1a,e, 5-HT 2, 5-HT 3) or mixed 5-HT 2- D 2 receptor antagonist; (c) selective dopamine agonists or partial agonists; and (d) sigma-site and excitatory amino-acid antagonists. Such compounds are at various stages of development. The only drug which has truly distinguished itself as ‘atypical’ is clozapine. Its mechanism of action is unknown and the search for it, in large part, has been the impetus for development of the compounds listed above.
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Second-generation atypical antipsychotics such as clozapine, risperidone, olanzapine, and quetiapine primarily affect DA and 5-HT systems, but with markedly reduced extrapyramidal side effects.
“Second-generation, or ‘atypical,’ antipsychotics, such as clozapine (which has affinity for D2 and D4 receptors [426]), risperidone, olanzapine, and quetiapine, primarily affect DA and 5-HT systems, but with markedly reduced extrapyramidal side effects [427].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [426]
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References 107 · Cited by 108
- Authors
- Lieberman, J. A.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Lieberman, Jeffrey A.
- Venue
- British Journal of Psychiatry
- Publisher
- Royal College of Psychiatrists
- Published
- 1993-12
- Volume
- 163
- Issue
- S22
- Pages
- 7-18
- ISSN
- 0007-1250 (ISSN-L)
- 1472-1465
- OpenAlex
- W2414875517
- Cited by
- 108
- References
- 107
- Citations by year
- 2024: 1 · 2023: 2 · 2019: 1 · 2018: 1 · 2017: 1 · 2015: 2 · 2013: 2 · 2012: 2
- FWCI
- 10.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The British Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH00537)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
- Keywords
- atypical antipsychotics, mechanism of action, clozapine, dopamine antagonists, serotonin receptor agonists, excitatory amino acid antagonists, antipsychotic drug development, adverse effects
- MeSH terms
- Clozapine, Humans, Antipsychotic Agents, Drugs, Investigational
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