Cited by 878Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

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Antipsychotic Drugs: Direct Correlation Between Clinical Potency and Presynaptic Action on Dopamine Neurons

Seeman, P., Lee, T.·1975·Science

DOI 10.1126/science.1145194

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Abstract

Neuroleptic (antipsychotic) drugs inhibited the electrically stimulated release of [3 H]dopamine from rat striatal slices. The concentrations for 50 percent inhibition (ranging from 11.5 nanomolar for spiroperidol to 800 nanomolar for thioridazine) correlated closely with the average daily dosages of 25 neuroleptic drugs used clinically for schizophrenia. The correlation includes butyrophenones, phenothiazines, reserpine, pimozide, clozapine, and (+)-butaclamol. Clinically inactive isomers [trans-thiothixene,trans-flupenthixol, and (-)-butaclamol] required 20 to 1000 times higher concentrations than the active isomers to inhibit release. Compared to the inhibition of [3 H]dopamine release, much higher neuroleptic concentrations were needed to inhibit the electrically stimulated release of other neurotransmitters—[3 H]acetylcholine, [3 H]GABA (γ-aminobutyric acid). The neuroleptic drugs may block the presynaptic coupling between impulse and neurosecretion.

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Authors: Seeman, P., & Lee, T.
Affiliations: University of Toronto (CA)
ORCID: Seeman, P.
Lee, T.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1975-06-20
Volume: 188
Issue: 4194
Pages: 1217-1219
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1145194
OpenAlex: W2006122360
Cited by: 869
References: 35
Citations by year: 2026: 5 · 2025: 8 · 2024: 13 · 2023: 16 · 2022: 22 · 2021: 13 · 2020: 18 · 2019: 36 · 2018: 21 · 2017: 30 · 2016: 26 · 2015: 28 · 2014: 37 · 2013: 23 · 2012: 32
FWCI: 62.55
Type: journal article
Language: en
Open access: closed
Locations: Science (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
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: antipsychotic drugs, presynaptic dopamine release, striatum, spiperone, thioridazine, butyrophenones, phenothiazines, reserpine, pimozide, clozapine, butaclamol, stereoisomers, acetylcholine release, GABA release, schizophrenia
MeSH terms: Acetylcholine, Animals, Corpus Striatum, Dopamine, Dose-Response Relationship, Drug, Electric Stimulation, gamma-Aminobutyric Acid, Haloperidol, Humans, Male, Neurons, Neurosecretion, Schizophrenia, Tranquilizing Agents, Tritium, Rats

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Antipsychotic Drugs: Direct Correlation Between Clinical Potency and Presynaptic Action on Dopamine Neurons

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