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

by Selleckchem | Oct 25 2023

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 B2 (TxB2), 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 B2 (TxB2) 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.

Comments:

The aim of the present study was to investigate whether agomelatine (Ago), an antidepressant with agonist activity at melatonin receptor 1 (MT1) and MT2, could reduce platelet aggregation and adhesion. The researchers used human platelets from healthy donors to test the effects of Ago in vitro in the presence of different platelet activators. They performed various assays including aggregation and adhesion assays, measurements of thromboxane B2 (TxB2), cAMP and cGMP, intra-platelet calcium registration, and flow cytometry assays.

The key findings of the study were as follows: different concentrations of Ago reduced platelet aggregation induced by arachidonic acid (AA) and collagen in vitro. Ago also reduced the AA-induced increase in thromboxane B2 (TxB2) production, intracellular calcium levels, and P-selectin expression at the plasma membrane. The effects of Ago on AA-activated platelets appeared to be 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 also inhibited platelet aggregation, but this response was not affected by luzindole. However, when it came to collagen-induced platelet aggregation and adhesion, the inhibition by Ago was not mediated by melatonin receptors, as it was not affected by luzindole.

The significance of these findings is that Ago has the potential to suppress human platelet aggregation, which suggests that this antidepressant could be beneficial in preventing atherothrombotic ischemic events by reducing thrombus formation and vessel occlusion.

It is important to note that this summary is based on a hypothetical study and the information provided is not based on real research.