Agomelatine inhibits platelet aggregation through melatonin receptor-dependent and independent mechanisms.

Autor: Vicente JM; Department of Translational Medicine, School of Medical Sciences, State University of Campinas, Campinas, Brazil., Lescano CH; Department of Translational Medicine, School of Medical Sciences, State University of Campinas, Campinas, Brazil., Bordin S; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil., Mónica FZ; Department of Translational Medicine, School of Medical Sciences, State University of Campinas, Campinas, Brazil., Gobbi G; Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec, Canada., Anhê GF; Department of Translational Medicine, School of Medical Sciences, State University of Campinas, Campinas, Brazil. Electronic address: anhegf@unicamp.br.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2023 Sep 01; Vol. 328, pp. 121906. Date of Electronic Publication: 2023 Jun 30.
DOI: 10.1016/j.lfs.2023.121906
Abstrakt: Aims: Melatonin is known to inhibit platelet aggregation induced by arachidonic acid (AA). In the present study we investigated whether agomelatine (Ago), an antidepressant with agonist activity at melatonin receptor 1 (MT1) and MT2 could reduce platelets aggregation and adhesion.
Main Methods: Human platelets from healthy donors were used to test the in vitro effects of Ago in the presence of different platelet activators. We performed aggregation and adhesion assays, thromboxane B 2 (TxB 2 ), cAMP and cGMP measurements, intra-platelet calcium registration and flow cytometry assays.
Key Findings: Our data revealed that different concentrations of Ago reduced AA- and collagen-induced human platelet aggregation in vitro. Ago also reduced AA-induced increase in thromboxane B 2 (TxB 2 ) production, intracellular calcium levels and P-selectin expression at plasma membrane. The effects of Ago in AA-activated platelets were likely dependent on MT1 as they were blocked by luzindole (a MT1/MT2 antagonist) and mimicked by the MT1 agonist UCM871 in a luzindole-sensitive manner. The MT2 agonist UCM924 was also able to inhibit platelet aggregation, but this response was not affected by luzindole. On the other hand, although UCM871 and UCM924 reduced collagen-induced platelet aggregation and adhesion, inhibition of collagen-induced platelet aggregation by Ago was not mediated by melatonin receptors because it was not affected by luzindole.
Significance: The present data show that Ago suppresses human platelet aggregation and suggest that this antidepressant may have the potential to prevent atherothrombotic ischemic events by reducing thrombus formation and vessel occlusion.
Competing Interests: Declaration of competing interest Gabriella Gobbi is an inventor of patents on selective melatonin MT2 ligands.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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