Structural modification of the antidepressant mianserin suggests that its anti-inflammatory activity may be independent of 5-Hydroxytryptamine receptors

Sacre, Sandra, Jaxa-Chamiec, Albert, Low, Caroline, Chamberlain, Giselle and Tralau-Stewart, Cathy (2019) Structural modification of the antidepressant mianserin suggests that its anti-inflammatory activity may be independent of 5-Hydroxytryptamine receptors. Frontiers in Immunology, 10 (1167). pp. 1-9. ISSN 1664-3224

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Abstract

Antidepressants are increasingly recognized to have anti-inflammatory properties in addition to their ability to treat major depressive disorders. To explore if engagement of 5-hydroxytryptamine (5-HT) receptors was required for the anti-inflammatory effect of the tetracyclic antidepressant mianserin, a series of structural derivatives were generated with the aim of reducing 5-HT receptor binding. Primary human peripheral blood mononuclear cells were used to screen for anti-inflammatory activity. The lead compound demonstrated a significant loss in 5-HT receptor binding, as assessed by non-selective 5-HT binding of radiolabelled serotonin in rat cerebral cortex. However, it retained the ability to inhibit endosomal toll-like receptor 8 signaling in primary human macrophages and spontaneous cytokine production from human rheumatoid synovial tissue equivalent to that previously observed for mianserin. These data demonstrate that the anti-inflammatory mechanism of mianserin may be independent of 5-HT receptor activity. This research offers new insights into the mechanism and structural requirements for the anti-inflammatory action of mianserin.

Item Type: Article
Keywords: inflammation, toll-like receptor, rheumatoid arthritis, antidepressant, mianserin, macrophage, 5-hydroxytryptamine, tumor necrosis factor
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
Subjects: Q Science > Q Science (General) > Q0179.9 Research
R Medicine > RM Therapeutics. Pharmacology > RM0300 Drugs and their actions
Depositing User: Sandra Sacre
Date Deposited: 25 Jun 2019 14:33
Last Modified: 01 Jul 2019 11:46
URI: http://sro.sussex.ac.uk/id/eprint/84574

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