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- W2144663862 abstract "Trifenagrel.HCl (trifenagrel) (2-[2-(2-dimethylaminoethoxy) phenyl]-4,5-diphenylimidazole monohydrochloride) is a chemically novel, potent inhibitor (IC50 = 0.3-3.0 microM) of arachidonate (AA)- and collagen-induced aggregation of platelets from several animal species and humans. When trifenagrel was administered p.o. to guinea pigs, there was a sustained (greater than 3 hr) inhibition of AA- and collagen-induced platelet aggregation ex vivo (1 hr ED50 = 1.4 and 9.4 mg/kg, respectively). In humans, trifenagrel inhibited the second phase of ADP-induced aggregation ex vivo up to 6 hr after a single dose of 100 to 300 mg p.o. The mechanism of action of trifenagrel appears to be a reversible inhibition of platelet AA cyclooxygenase. Doses of trifenagrel up to 100 mg/kg p.o. in rats and guinea pigs inhibited gastric mucosal AA cyclooxygenase but did not produce the gastric damage associated with the administration of other cyclooxygenase inhibitors such as aspirin and indomethacin. To our knowledge this is the first report of a compound which inhibits gastric mucosal prostaglandin levels but causes little or no gastrointestinal (g.i.) irritation in rodents. Although trifenagrel caused g.i. irritation in dogs and humans, the nature of the damage suggests that the compound may have acted as a local irritant in these species. Furthermore, compared to aspirin trifenagrel produced significantly less gastric irritation and fecal blood loss in humans. The physiochemical properties of trifenagrel may be important for the lack of g.i. irritation in rodents and for the diminished damage relative to aspirin in humans." @default.
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- W2144663862 date "1989-05-01" @default.
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- W2144663862 title "Trifenagrel: a chemically novel platelet aggregation inhibitor." @default.
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