The antiplatelet activity of PMC, a potent α‐tocopherol analogue, is mediated through inhibition of cyclo‐oxygenase

PMC, a potent α‐tocopherol derivative, dose‐dependently (5–25 μ M ) inhibited the ATP‐release reaction and platelet aggregation in washed human platelets stimulated by agonists (collagen and ADP). PMC also dose‐dependently inhibited the intracellular Ca 2+ mobilization, whereas it did not inhibit phosphoinositide breakdown in human platelets stimulated by collagen. PMC (10 and 25 μ M ) significantly inhibited collagen‐stimulated thromboxane A 2 (TxA 2 ) formation in human platelets. On the other hand, PMC (25 and 100 μ M ) did not increase the formation of cyclic AMP or cyclic GMP in platelets. Moreover, PMC (25, 100, and 200 μ M ) did not affect the thromboxane synthetase activity of aspirin‐treated platelet microsomes. PMC (10 and 25 μ M ) markedly inhibited the exogenous arachidonic acid (100 μ M )‐induced prostaglandin E 2 (PGE 2 ) formation in the presence of imidazole (600 μ M ) in washed human platelets, indicating that PMC inhibits cyclo‐oxygenase activity. We conclude that PMC may exert its anti‐platelet aggregation activity by inhibiting cyclo‐oxygenase activity, which leads to reduced prostaglandin formation; this, in turn, is followed by a reduction of TxA 2 formation, and finally inhibition of [Ca 2+ ] i mobilization and ATP‐release.British Journal of Pharmacology (1999) 127 , 1206–1212; doi: 10.1038/sj.bjp.0702637