Albayrak, YakupHashimoto, Kenji2022-05-112022-05-112017978-3-319-50174-1978-3-319-50172-70065-25982214-8019https://doi.org/10.1007/978-3-319-50174-1_11https://hdl.handle.net/20.500.11776/9063Accumulating 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.en10.1007/978-3-319-50174-1_11info:eu-repo/semantics/closedAccessDonepezilIfenprodilFluvoxaminePsychiatric diseasesSerotonin Reuptake InhibitorsImproved Cognitive ImpairmentsPositron-Emission-TomographyH-3 Ifenprodil BindingDouble-BlindDelusional DepressionSchizophrenia ReportTardive-DyskinesiaNeurite OutgrowthTherapeutic DrugsBook Chapter964153161N/AWOS:0004123156000122-s2.0-8501590060728315270Q3