Cited by 372Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorMental Health and Psychiatry

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5-HT2and D2Receptor Occupancy of Olanzapine in Schizophrenia: A PET Investigation

Kapur, Shitij, Zipursky, Robert B., Remington, Gary, Jones, Corey, DaSilva, Jean, Wilson, Alan A., Houle, Sylvain·1998·American Journal of Psychiatry

DOI 10.1176/ajp.155.7.921

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Abstract

OBJECTIVE: Olanzapine is a new atypical antipsychotic recently introduced for the treatment of schizophrenia. The purpose of this study was to investigate olanzapine's binding to the serotonin 5-HT2 and dopamine D2 receptors in schizophrenic patients being treated with clinically relevant doses. METHOD: Twelve patients with schizophrenia were randomly assigned to 5, 10, 15, or 20 mg/day of olanzapine in a prospective fashion. Three other subjects taking 30-40 mg/day were also included. Once steady-state plasma levels were achieved, dopamine D2 and serotonin 5-HT2 receptors were assessed by using [11C]raclopride and [18F]setoperone positron emission tomography imaging, respectively. Ratings of clinical status, extrapyramidal side effects, and prolactin levels were also obtained. RESULTS: Olanzapine induced near saturation of the 5-HT2 receptors, even at 5 mg/day. Its D2 occupancy increased with dose: patients taking 5-20 mg/day showed 43%-80% D2 occupancy, while patients taking 30-40 mg/day showed 83%-88%. CONCLUSIONS: Olanzapine is a potent 5-HT2 blocker and shows a higher 5-HT2 than D2 occupancy at all doses. However, its D2 occupancy is higher than that of clozapine and similar to that of risperidone. In the usual clinical dose range of 10-20 mg/day, its occupancy varies from 71% to 80%, and this restricted range may explain its freedom from extrapyramidal side effects and prolactin elevation. However, doses of 30 mg/day and higher are associated with more than 80% D2 occupancy and may have a higher likelihood of prolactin elevation and extrapyramidal side effects.

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Authors: Kapur, S., Zipursky, R. B., Remington, G., Jones, C., DaSilva, J., Wilson, A. A., & Houle, S.
ORCID: Kapur, Shitij
Zipursky, Robert B.
Remington, Gary
DaSilva, Jean
Houle, Sylvain
Venue: American Journal of Psychiatry
Publisher: American Psychiatric Association Publishing
Published: 1998-07-01
Volume: 155
Issue: 7
Pages: 921-928
ISSN: 0002-953X (ISSN-L)
1535-7228
DOI: 10.1176/ajp.155.7.921
OpenAlex: W2163010981
Cited by: 370
References: 41
Citations by year: 2026: 5 · 2025: 7 · 2024: 9 · 2023: 9 · 2022: 8 · 2021: 4 · 2020: 10 · 2019: 5 · 2018: 7 · 2017: 6 · 2016: 8 · 2015: 7 · 2014: 9 · 2013: 19 · 2012: 14
FWCI: 15.00
Type: journal article
Language: en
Open access: closed
Locations: American Journal of 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
Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
Keywords: olanzapine, schizophrenia, dopamine D2 receptor occupancy, atypical antipsychotics, dose dependence, extrapyramidal symptoms, prolactin elevation, [11C]raclopride, clozapine, risperidone
MeSH terms: Olanzapine, Adult, Benzodiazepines, Carbon Radioisotopes, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Fluorine Radioisotopes, Humans, Male, Pirenzepine, Prolactin, Pyrimidinones, Receptors, Serotonin, Salicylamides, Schizophrenia, Tomography, Emission-Computed, Antipsychotic Agents, Treatment Outcome, Receptors, Dopamine D2, Raclopride

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5-HT2and D2Receptor Occupancy of Olanzapine in Schizophrenia: A PET Investigation

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