Effects of terbogrel on platelet function and prostaglandin endoperoxide transfer

The present study describes the platelet-inhibitory effects of terbogrel (5-hexenoic acid, 6-[3-[[(cyanoamino)[( 1,1-dimethylethyl)amino]methylene]amino]phenyl]-6-(3-pyridinyl)- (epsilon)-), a novel combined thromboxane A(2) synthase inhibitor and thromboxane A(2) receptor antagonist. Terbogrel concentration-dependently inhibited collagen (0.6 mu g/ml)- and U46619 (11 alpha,9 alpha-epoxymethano-15(S)-hydroxy-prosta-5Z, 13 E-dienoic acid) (1 mu M)-induced aggregation and thromboxane synthesis of washed human platelets. Ln this system, terbogrel exhibited an equipotent (IC50 of about 10 nM) activity as thromboxane A(2) synthase inhibitor and thromboxane A(2) receptor antagonist. In addition, the compound favoured prostacyclin synthesis in cultured vascular smooth muscle cells by increasing the transfer of platelet-derived prostaglandin endoperoxides. Terbogrel appears to be a compound with an equipotent molar potency as thromboxane A(2) synthase inhibitor and receptor antagonist. (C) 1998 Elsevier Science B.V.