Abstract
The atypical neuroleptic clozapine is thought to exert its psychopharmacological actions through a variety of neurotransmitter receptors. It binds preferentially to D4 and 5-HT2 receptors; however, little is known on it's interaction with the 5-HT3 receptor. Using a cell line stably expressing the 5-HT3 receptor, whole-cell voltage-clamp analysis revealed functional antagonistic properties of clozapine at low nanomolar concentrations in view of a binding affinity in the upper nanomolar range. Because the concentration of clozapine required for an interaction with the 5-HT3 receptor can be achieved with therapeutical doses, functional antagonistic properties at this ligand-gated ion channel may contribute to its unique psychopharmacological profile.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antipsychotic Agents / administration & dosage
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Antipsychotic Agents / metabolism
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Antipsychotic Agents / pharmacology*
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Binding, Competitive
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Cell Line
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Clozapine / administration & dosage
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Clozapine / metabolism
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Clozapine / pharmacology*
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Dose-Response Relationship, Drug
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Humans
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Imidazoles / metabolism
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Indoles / metabolism
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Ion Channel Gating
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Ion Channels / drug effects
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Ion Channels / metabolism
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Ligands
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Receptors, Serotonin / drug effects*
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Receptors, Serotonin / metabolism
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Receptors, Serotonin, 5-HT3
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Serotonin Antagonists / administration & dosage
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Serotonin Antagonists / metabolism
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Serotonin Antagonists / pharmacology*
Substances
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Antipsychotic Agents
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Imidazoles
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Indoles
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Ion Channels
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Ligands
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Receptors, Serotonin
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Receptors, Serotonin, 5-HT3
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Serotonin Antagonists
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GR 65630
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Clozapine