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The Serotonin 1A (5-HT1A) Receptor as a Pharmacological Target in Depression.
- Source :
- CNS Drugs; Jul2023, Vol. 37 Issue 7, p571-585, 15p
- Publication Year :
- 2023
-
Abstract
- Clinical depression is a common, debilitating and heterogenous disorder. Existing treatments for depression are inadequate for a significant minority of patients and new approaches are urgently needed. A wealth of evidence implicates the serotonin 1A (5-HT<subscript>1A</subscript>) receptor in the pathophysiology of depression. Stimulation of the 5-HT<subscript>1A</subscript> receptor is an existing therapeutic target for treating depression and anxiety, using drugs such as buspirone and tandospirone. However, activation of 5-HT<subscript>1A</subscript> raphe autoreceptors has also been suggested to be responsible for the delay in the therapeutic action of conventional antidepressants such as selective serotonin reuptake inhibitors (SSRIs). This narrative review provides a brief overview of the 5-HT<subscript>1A</subscript> receptor, the evidence implicating it in depression and in the effects of conventional antidepressant treatment. We highlight that pre- and post-synaptic 5-HT<subscript>1A</subscript> receptors may have divergent roles in the pathophysiology and treatment of depression. To date, developing this understanding to progress therapeutic discovery has been limited, partly due to a paucity of specific pharmacological probes suitable for use in humans. The development of 5-HT<subscript>1A</subscript> 'biased agonism', using compounds such as NLX-101, offers the opportunity to further elucidate the roles of pre- and post-synaptic 5-HT<subscript>1A</subscript> receptors. We describe how experimental medicine approaches can be helpful in profiling the effects of 5-HT<subscript>1A</subscript> receptor modulation on the different clinical domains of depression, and outline some potential neurocognitive models that could be used to test the effects of 5-HT<subscript>1A</subscript> biased agonists. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 11727047
- Volume :
- 37
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- CNS Drugs
- Publication Type :
- Academic Journal
- Accession number :
- 167361093
- Full Text :
- https://doi.org/10.1007/s40263-023-01014-7