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Text
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<a href="http://doi.org/10.1038/sj.tpj.6500418" target="_blank" rel="noreferrer">http://doi.org/10.1038/sj.tpj.6500418</a>
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Title
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No evidence for binding of clozapine, olanzapine and/or haloperidol to selected receptors involved in body weight regulation.
Publisher
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Pharmacogenomics Journal
Date
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2007
Subject
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Humans; Animals; Protein Binding; IM; Receptors; Antipsychotic Agents/me [Metabolism]; Antipsychotic Agents/pd [Pharmacology]; Benzodiazepines/me [Metabolism]; Benzodiazepines/pd [Pharmacology]; Body Weight/de [Drug Effects]; Cell Surface/me [Metabolism]; Clozapine/me [Metabolism]; Clozapine/pd [Pharmacology]; Haloperidol/me [Metabolism]; Haloperidol/pd [Pharmacology]; Radioligand Assay
Creator
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Theisen FM; Haberhausen M; Firnges MA; Gregory P; Reinders JH; Remschmidt H; Hebebrand J; Antel J
Description
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The underlying mechanisms of antipsychotic (AP)-induced weight gain are unknown, but both central and peripheral AP target receptors could potentially be involved. This study used radioligand binding assays to compare the binding affinities of clozapine, olanzapine and haloperidol for candidate receptors potentially involved in AP-induced weight gain. Selected candidates derived from known pathways involved in body weight regulation included receptors classified as anorexigenic (bombesin receptor subtype 3, calcitonin gene-related peptide receptor, cholecystokinin receptor, melanocortin-4 receptor, neurotensin receptor 1) or orexigenic (cannabinoid receptor 1, galanin 1 receptor, melanin-concentrating hormone receptor (MCHR), neuropeptide Y1 receptor) as well as receptors involved in physiological actions related to digestion and fluid homeostasis (angiotensin II type 1 receptor, bradykinin B2 receptor, endothelin receptor, neurokinin 1 receptor, vasoactive intestinal polypeptide receptor 1). Clozapine, olanzapine and haloperidol exhibited negligible affinities to all of these receptors except for the MCHR (Ki=501 nM; haloperidol). With respect to other candidates from (neuro)transmitter systems already suggested to be involved in AP-induced weight gain, the binding profile of olanzapine resembled that of clozapine, with high affinity (Ki<10 nM) for serotonin (5-HT) 5-HT2A, 5-HT2C and 5-HT6, muscarinic M1 and histamine H1 receptors. In contrast, the binding profile of haloperidol was substantially different (high affinity only for the dopamine D1 receptor). In conclusion, we have not identified a novel binding site of the two investigated atypical AP that could contribute to the induced weight gain.
2007
Identifier
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<a href="http://doi.org/10.1038/sj.tpj.6500418" target="_blank" rel="noreferrer">10.1038/sj.tpj.6500418</a>
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Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Type
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Journal Article
2007
Animals
Antel J
Antipsychotic Agents/me [Metabolism]
Antipsychotic Agents/pd [Pharmacology]
Backlog
Benzodiazepines/me [Metabolism]
Benzodiazepines/pd [Pharmacology]
Body Weight/de [Drug Effects]
Cell Surface/me [Metabolism]
Clozapine/me [Metabolism]
Clozapine/pd [Pharmacology]
Firnges MA
Gregory P
Haberhausen M
Haloperidol/me [Metabolism]
Haloperidol/pd [Pharmacology]
Hebebrand J
Humans
IM
Journal Article
Pharmacogenomics Journal
Protein Binding
Radioligand Assay
Receptors
Reinders JH
Remschmidt H
Theisen FM