title: Activation of sigma-1 receptor chaperone in the treatment of neuropsychiatric diseases and its clinical implication.
abstract: Endoplasmic reticulum (ER) protein sigma-1 receptor represents unique chaperone activity in the central nervous system, and it exerts a potent influence on a number of neurotransmitter systems. Several lines of evidence suggest that activation of sigma-1 receptor plays a role in the pathophysiology of neuropsychiatric diseases, as well as in the mechanisms of some therapeutic drugs and neurosteroids. Preclinical studies showed that some selective serotonin reuptake inhibitors (SSRIs; fluvoxamine, fluoxetine, excitalopram), donepezil, and ifenprodil act as sigma-1 receptor agonists. Furthermore, sigma-1 receptor agonists could improve the N-methyl-D-aspartate (NMDA) antagonist phencyclidine (PCP)-induced cognitive deficits in mice. A study using positron emission tomography have demonstrated that an oral administration of fluvoxamine or donepezil could bind to sigma-1 receptor in the healthy human brain, suggesting that sigma-1 receptor might be involved in the therapeutic mechanisms of these drugs. Moreover, case reports suggest that sigma-1 receptor agonists, including fluvoxamine, and ifenprodil, may be effective in the treatment of cognitive impairment in schizophrenia, delirium in elderly people, and flashbacks in post-traumatic stress disorder. In this review article, the author would like to discuss the clinical implication of sigma-1 receptor agonists, including endogenous neurosteroids, in the neuropsychiatric diseases.
authors.affiliation: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan. Electronic address: hashimoto@faculty.chiba-u.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D000077265:Donepezil; D006801:Humans; D007189:Indans / Q000494:pharmacology*; D001523:Mental Disorders / Q000188:drug therapy* / Q000503:physiopathology*; D008959:Models, Neurological; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D017480:Receptors, sigma / Q000819:agonists* / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000097605:Sigma-1 Receptor
chemical_list: D000077265:Donepezil; D007189:Indans; D018377:Neurotransmitter Agents; D010880:Piperidines; D017480:Receptors, sigma; D017367:Selective Serotonin Reuptake Inhibitors; D000097605:Sigma-1 Receptor; C010739:ifenprodil
keywords: Cognition; Delirium; Neuroplasticity; Neuroprotection; Sigma-1 receptor chaperone