Review
doi: 10.1016/j.pharmthera.2010.04.003. Epub 2010 May 11.Sigma receptors: potential targets for a new class of antidepressant drug
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- PMID:20438757
- PMCID: PMC3993947
- DOI: 10.1016/j.pharmthera.2010.04.003
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Review
Sigma receptors: potential targets for a new class of antidepressant drug
James A Fishback et al. Pharmacol Ther.2010 Sep.
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Abstract
Despite the widespread and devastating impact of depression on society, our current understanding of its pathogenesis is limited. Likewise, existing treatments are inadequate, providing relief to only a subset of people suffering from depression. The search for more effective antidepressant drugs includes the investigation of new molecular targets. Among them, current data suggests that sigma receptors are involved in multiple processes effecting antidepressant-like actions in vivo and in vitro. This review summarizes accumulated evidence supporting a role for sigma receptors in antidepressant effects and provides a conceptual framework for delineating their potential roles over the course of antidepressant treatment.
2010 Elsevier Inc. All rights reserved.
Conflict of interest statement
The authors have no conflicts of interest to disclose.
Figures
Classic antidepressant drugs produce effects which can be classified temporally into immediate, intermediate and delayed actions, with resulting functional changes associated at each stage.
It is believed that Ca2+ modulation through sigma receptors can act upon pathways involved in neurite outgrowth, as well as gene regulation, specifically, ERK, MAPK and Akt pathways. It is hypothesized that sigma receptor-mediated modulation of IP3Rs at the MAM, also contributes to an increase in ATP production from the mitochondria, which may have profound effects on signaling within the cell which have not yet been fully studied. Sigma receptors have also been shown to modulate PKA pathways; sigma agonists have been shown to modulate the phosphorylation of CREB, indicative of effects on gene transcription. Sigma receptors also have known effects on the transmission of signaling via neurotransmitters; however these pathways have not been fully elucidated. Dashed lines indicate known and hypothesized effects of sigma receptors on signaling pathways believed to be involved in depression.
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