Effects of oral administration of ticagrelor on the plasma level of adrenaline, histamine, serotonin, and acetylcholine in rat

Background: Ticagrelor as a reversible P2Y12 receptor antagonist which plays an important role in the treatment of acute coronary syndrome (ACS). Dyspnea is one of the main adverse reactions of ticagrelor, however the mechanism is not clearly now. The aim of this study was to assess the possible relationship between ticagrelor-related dyspnea and some neurotransmitter in plasma which can contract the bronchial smooth muscle.Methods: The effects of ticagrelor on the plasma level of adrenaline, histamine, serotonin, and acetylcholine was studied in rats. Ticagrelor was administered at a loading dose of 24 mg/kg for the first time, and then maintenance dose 12 mg/kg, twice a day for 6 days. The plasma level of adrenaline, histamine, serotonin, and acetylcholine was determined by LC-MS/MS.Results: The plasma level of serotonin increased after ticagrelor administrating, especially at 1.5h ( p <0.05) reach the level of statistical significance. The level of serotonin in plasma was consistent with ticagrelor blood concentration. Meanwhile, ticagrelor can cause a decrease in the plasma concentration of histamine, and the change was statistically significant at time points of 1.5h, 3.5h and 10.5h respectively. The concentration of the adrenaline and acetylcholine had no change.Conclusions: The results of this study reveal that ticagrelor can increases blood serotonin levels and this may be a cause of dyspnea ticagrelor-related.