Activation of sigma-1 receptor chaperone in the treatment of neuropsychiatric diseases and its clinical implication

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. © 2014 japanese pharmacological society.