Sigma-1 Receptor Agonists and Their Clinical Implications in Neuropsychiatric Disorders.
Accumulating evidence suggests that sigma-1 receptors play a role in the pathophysiology of neuropsychiatric diseases, as well as in the mechanisms of some selective serotonin reuptake inhibitors (SSRIs). Among the SSRIs, the order of affinity for sigma-1 receptors is as follows: fluvoxamine > sertraline > fluoxetine > escitalopram > citalopram >> paroxetine. Some SSRIs (e.g., fluvoxamine, fluoxetine and escitalopram) and other drugs (donepezil , ifenprodil , dehydroepiandeterone (DHEA)) potentiate nerve-growth factor (NGF)-induced neurite outgrowth in PC12 cells, and these effects could be antagonized by the selective sigma-1 receptor antagonist NE-100. Furthermore, fluvoxamine, donepezil, and DHEA, but not paroxetine or sertraline, improved phencyclidine-induced cognitive deficits in mice, and these effects could be antagonized by NE-100. Several clinical studies showed that sigma-1 receptor agonists such as fluvoxamine and ifenprodil could have beneficial effects in patients with neuropsychiatric disorders. In this chapter, the authors will discuss the role of sigma-1 receptors in the mechanistic action of some SSRIs, donepezil, neurosteroids, and ifenprodil, and the clinical implications for sigma-1 receptor agonists .
Namik Kemal University, Tekirdag, Turkey.
Yakup
Y
Albayrak
Chiba University, Chiba, Japan. hashimoto@faculty.chiba-u.jp.
Kenji
K
Hashimoto
D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D017480:Receptors, sigma / Q000819:agonists* / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D000097605:Sigma-1 Receptor
D017480:Receptors, sigma; D017367:Selective Serotonin Reuptake Inhibitors; D000097605:Sigma-1 Receptor
Donepezil; Fluvoxamine; Ifenprodil; Psychiatric diseases