Aguchi, Japan). Ticagrelor was synthesized by Chemtech Labo, Inc. (Tokyo, Japan). AR-C124910XX was synthesized by Daiichi Sankyo RD Novare Co., Ltd. (Tokyo, Japan). Prasugrel and ticagrelor were suspended in 5 (w/v) solution of gum Arabic (Wako Pure Chemical Industries, Osaka, Japan). Prasugrel, ticagrelor and car (five gum Arabic remedy) were orally administered to non-fasted rats inside a volume of 1 mL g-1. The supply of other reagents was as follows: ADP sodium salt and collagen (LMS Co., Ltd., Tokyo, Japan).ResultsADP-induced platelet aggregation in vitroIn the automobile group of every test agent, imply platelet aggregations ranged from 52 to 59 for five mmol -1 ADP84 British Journal of Pharmacology (2013) 169 82?A comparison of pharmacological profiles of prasugrel and ticagrelorBJPADP concentration-response for ex vivo platelet aggregationThe inhibitory effects of prasugrel and ticagrelor on platelet aggregation induced by larger concentrations of ADP (50 and 200 mmol -1) had been also determined at the time of peak impact, four h just after dosing. Prasugrel (1 or 3 mg g-1) significantly inhibited platelet aggregation induced by ADP at all concentrations tested in a dose-related manner, as well as the effectwas not reversed by growing the concentration of ADP (Figure two).Price of 1212086-74-2 Ticagrelor (3 or ten mg g-1) also showed significant inhibition of platelet aggregation induced by ADP at all concentrations utilised, and, similarly, the effect of ticagrelor on ADP-induced aggregation appeared to become insurmountable, with no tested concentration of ADP completely overcoming the inhibition (Figure two).1S,2S-DHAC-Phenyl Trost Ligand Order Collagen-induced ex vivo platelet aggregationIn addition to ADP-induced platelet aggregation, inhibitory effects of prasugrel and ticagrelor on collagen-induced platelet aggregation (five mg L-1) had been determined four h soon after dosing. Each prasugrel (0.three? mg g-1) and ticagrelor (1?0 mg g-1) inhibited collagen-induced platelet aggregation inside a doserelated manner, with significant inhibitory effects getting observed right after 1 or three mg g-1 prasugrel and 3 or ten mg g-1 ticagrelor (Figure 3).PMID:23724934 AV shunt thrombosisThe anti-thrombotic effects of prasugrel and ticagrelor in vivo were assessed in the rat AV shunt thrombosis model. Prasugrel (0.three? mg g-1) and ticagrelor (1?0 mg g-1) had been orally administered, and blood was permitted to circulate via the shunt 4 h right after dosing. Thrombus weight within the vehicletreated group was 45.9 1.3 mg. Prasugrel considerably reduced thrombus weight at doses of 1 and 3 mg g-1 in a dose-related manner, compared with that inside the vehicletreated group with an ED50 worth of 1.8 mg g-1. Ticagrelor also considerably decreased the thrombus weight at doses of 3 and 10 mg g-1 with an ED50 value of 7.7 mg g-1 (Figure 4A).Bleeding timeFigureEx vivo effects of single doses of prasugrel (A) or ticagrelor (B) on platelet aggregation induced by ADP in rats. Agents had been orally administered to rats and blood was collected 1, 2, four, eight, 12 and 24 h just after dosing. Ex vivo platelet aggregation in PRP was induced by 20 mmol -1 ADP. Benefits are presented as the imply SEM (n = five). *P 0.05, **P 0.01, drastically distinctive from vehicle (Dunnett’s test).Effects of prasugrel (0.three? mg g-1) and ticagrelor (0.three?10 mg g-1) on the bleeding time in rats had been determined 4 h after administration of car, prasugrel or ticagrelor (Figure 4B). Prasugrel and ticagrelor every single substantially prolonged bleeding time at 1 mg g-1 or greater doses, compared with the car group (84 four s). Doses causing a twofol.