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]pheny l]-6-(3-pyridinyl)-, (epsilon)-), a novel combined thromboxane A2 synthase inhibitor and thromboxane A2 receptor antagonist. Terbogrel concentration-dependently inhibited collagen (0.6 microg/ml)- and U46619 (11alpha,9alpha-epoxymethano-15(S)-hydroxy-prosta-5Z,+ ++13E-dienoic acid) (1 microM)-induced aggregation and thromboxane synthesis of washed human platelets. In this system, terbogrel exhibited an equipotent (IC50 of about 10 nM) activity as thromboxane A2 synthase inhibitor and thromboxane A2 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 A2 synthase inhibitor and receptor antagonist.
Muck
S
S
Institut für Pharmakologie, Heinrich-Heine-Universität, Düsseldorf, Germany.
Weber
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AA
Schrör
K
K
D001792:Blood Platelets / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011449:Prostaglandin Endoperoxides / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D011449:Prostaglandin Endoperoxides; D011725:Pyridines; D017482:Receptors, Thromboxane; C112331:terbogrel; D013930:Thromboxane-A Synthase