In vitro effects of acetaminophen and its analogues on human platelet aggregation and thromboxane B2 synthesis.
We examined the effect of acetaminophen and the structural analogues 2,6-dimethylacetaminophen, 3,5-dimethylacetaminophen, and N-acetyl-p-benzoquinone imine on human platelet aggregation, 14C-serotonin secretion, and thromboxane B2 synthesis. Preincubation with 1 mM acetaminophen for 2 min completely inhibited arachidonic acid- and collagen-stimulated platelet aggregation. Thromboxane B2 production and 14C-serotonin secretion by arachidonic acid-stimulated platelets also were completely inhibited. Preincubation of platelets with 1 mM 3,5-dimethylacetaminophen inhibited collagen and arachidonic acid-induced aggregation and arachidonic acid-stimulated thromboxane B2 synthesis, while treatment with 2,6-dimethylacetaminophen did not inhibit aggregation and blocked thromboxane B2 formation to a much lesser degree. Preincubation with 1 mM N-acetyl-p-benzoquinone imine inhibited arachidonic acid-induced aggregation and 14C-serotonin secretion but had no effect on arachidonic acid-induced thromboxane B2 formation and collagen-induced platelet aggregation.
D000082:Acetaminophen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
D001095:Arachidonic Acids; D013931:Thromboxanes; C042524:3',5'-dimethylacetaminophen; D016718:Arachidonic Acid; D012701:Serotonin; D000082:Acetaminophen; D013929:Thromboxane B2; C045360:2,6-dimethylacetaminophen