The effect of agomelatine in human platelets aggregation and adhesion

Abstract

Several studies linked depression as an independent risk factor for the onset of cardiovascular disease. One reason for this correlation is the exacerbation of platelet activity described in patients diagnosed with Major Depressive Disorder (MDD). Among the therapeutic possibilities for depressed patients, selective serotonin reuptake inhibitors (SSRIs) demonstrate anti-aggregating ability. However, this class of drugs leads to a series of side effects that hinder their therapeutic use. Agomelatine, a drug with melatoninergic properties, is an option for treating DDM. Its differential is the agonist property of MT1 and MT2 receptors in parallel to the blockade of 5-HT2C serotonergic receptors. Although there are reports that platelet aggregation is inhibited by melatonin and potentiated by serotonin, it has not been established whether Agomelatine is capable of interfering with human platelet functional parameters. Thus, this study aims to analyze whether Agomelatine has the ability to inhibit platelet activity. We want to clarify whether these possible effects are due to either activation of MT1 / 2 receptors or blocking 5-HT2C receptors. Venous blood samples from 30 healthy 18- to 60-year-old male volunteers will be used to obtain platelet-rich plasma (PRP) and washed platelets for the execution of agonist-induced platelet aggregation assays (collagen, thrombin, ADP with or without Serotonin), platelet adhesion, quantification of Reactive Oxygen Species (ROS), change in conformation of integrin GPIIb / IIIa (±IIb²ƒ) by flow cytometry and intracellular calcium concentration ([Ca 2+]). (AU)