"Dopamine System Stabilizers, Aripiprazole, and the Next Generation of Antipsychotics, Part 1: "Goldilocks" Actions at Dopamine Receptors: (Brainstorms)
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Article AbstractBrainstorms: Psychosis occurs when too much dopamine exists in the synapses, and the action, akin to Goldilocks's first bowl of soup, is "too hot." Every antipsychotic that reduces the positive symptoms of psychosis such as delusions and hallucinations does so by blocking dopamine D2 receptors, most likely those of the mesolimbic dopamine pathway. Unfortunately, the blocking is often nonspecific, which is typical of conventional antipsychotic actions. Thus, when D2 receptors in the nigrostriatal dopamine pathway are also blocked, a penalty is paid in motor side effects, namely extrapyramidal reactions, pseudoparkinsonism, and ultimately, tardive dyskinesia.
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Third-generation antipsychotics such as aripiprizole are partial D2 receptor agonists with high affinity and low intrinsic activity, and may act as DA stabilizers.
“Finally, third-generation antipsychotics, such as aripiprizole, are partial D2 receptor agonists with high affinity and low intrinsic activity, and these drugs may act as ‘DA stabilizers’ because of their ability to stabilize, rather than simply upregulate or downregulate functional output of DA systems [428].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [428]
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Sugawara, H., Koyama, A., Maruyama, T., Koda, Y., Fukunaga, H., Ishikawa, T., Takebayashi, M., Okamoto, K., Fukui, T., & Hashimoto, M. (2022) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.13446 · Cited by 5 · see citing works
Methylphenidate-Induced Neuroleptic Malignant Syndrome
Basil, B., Mathews, M., & Budur, K. (2006) · The Primary Care Companion For CNS Disorders · doi:10.4088/pcc.v08n0109a · Cited by 5 · see citing works
- Authors
- Stahl, S. M.
- Affiliations
- Neuroscience Education Institute (US)
- Corresponding author
- Stahl, Stephen M.
- ORCID
- Stahl, Stephen M.
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2001-11-15
- Volume
- 62
- Issue
- 11
- Pages
- 841-842
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W2091915431
- Cited by
- 143
- References
- 1
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 6 · 2022: 8 · 2021: 6 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 1 · 2016: 5 · 2015: 2 · 2014: 6 · 2013: 3 · 2012: 10
- FWCI
- 5.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- 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 › Treatment of Major Depression
- Keywords
- aripiprazole, dopamine D2 receptor, dopamine agonists, antipsychotic drugs, psychosis, mesolimbic dopamine system, nigrostriatal dopamine pathway, extrapyramidal symptoms, tardive dyskinesia, positive symptoms
- MeSH terms
- Aripiprazole, Binding Sites, Corpus Striatum, Humans, Piperazines, Psychotic Disorders, Substantia Nigra, Antipsychotic Agents, Dopamine Agents, Quinolones, Receptors, Dopamine D2
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