EFFECTS OF TERBOGREL ON PLATELET-FUNCTION AND PROSTAGLANDIN ENDOPEROXIDE TRANSFER

The present study describes the platelet-inhibitory effects of terbogr el (5-hexenoic acid, 6-[3-[[(cyanoamino)[( hyl)amino]methylene]amino]p henyl]-6-(3-pyridinyl)- (epsilon)-), a novel combined thromboxane A(2) synthase inhibitor and thromboxane A(2) receptor antagonist. Terbogre l concentration-dependently inhibited collagen (0.6 mu g/ml)- and U466 19 (11 alpha,9 alpha-epoxymethano-15(S)-hydroxy-prosta-5Z, 13 E-dienoi c acid) (1 mu M)-induced aggregation and thromboxane synthesis of wash ed 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 fa voured prostacyclin synthesis in cultured vascular smooth muscle cells by increasing the transfer of platelet-derived prostaglandin endopero xides. Terbogrel appears to be a compound with an equipotent molar pot ency as thromboxane A(2) synthase inhibitor and receptor antagonist. ( C) 1998 Elsevier Science B.V.