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BY-NC-ND 3.0 license Open Access Published by De Gruyter Open Access August 28, 2012

Roles of σ1 receptors in the mechanisms of action of CNS drugs

  • Jun Toyohara EMAIL logo , Muneyuki Sakata and Kiichi Ishiwata

Abstract

Accumulating evidence suggests that σ1 receptors play a role in the mechanisms of action of some therapeutic drugs, such as the selective serotonin reuptake inhibitors (SSRIs), donepezil, and ifenprodil. Among the SSRIs, fluvoxamine, a potent σ1 receptor agonist, has the highest affinity for σ1 receptors, while donepezil and ifenprodil also show high affinity for σ1 receptors. These drugs affect neuronal plasticity indicated by potentiation of nerve-growth factor (NGF)-induced neurite outgrowth in PC12 cells. Furthermore, phencyclidine (PCP)-induced cognitive impairment, associated with animal models of schizophrenia, is significantly improved by sub-chronic administration of fluvoxamine and donepezil. These pharmacological actions are antagonised by treatment with the selective σ1 receptor antagonist NE-100. Positron emission tomography (PET) with the σ1 specific ligand carbon-11-labelled 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine ([11C]SA4503) indicated that fluvoxamine and donepezil can bind to σ1 receptors in the healthy human brain in a dose-dependent manner. These findings suggest that σ1 receptors may be involved in the mechanisms of action of some therapeutic drugs.

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Published Online: 2012-8-28
Published in Print: 2012-9-1

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