Inhibition of platelet thromboxane synthetase by 1-(3-benzyloxy-1[E]octenyl)imidazole.
1-(3-Benzyloxy-1[E]octenyl)imidazole (CBS-645) is a specific inhibitor of thromboxane synthetase. It inhibits the platelet enzyme in human and rabbit at micromolar concentrations. At a dose of 12.5 mg kg-1 in rabbits, CBS-645 displays a prolonged inhibitory effect on the formation of thromboxane (Tx) B2 induced by blood coagulation in vitro. In human volunteers, an oral dose of 50 mg leads to an average 70% inhibition of TxB2 formation. CBS-645 administered at a dose of 25 mg kg-1 p.o. in the rat, significantly increases bleeding time. In another test in which platelet interaction with the vessel wall is involved, i.e. in vivo platelet deposition onto desendothelialized aorta in the rabbit, the drug shows antithrombotic activity after a single oral administration of 5 mg kg-1. CBS-645 could be of interest in the treatment of the various diseases in which the pathological role of thromboxane A2 is suspected.
Sincholle
D
D
Coquelet
C
C
Bonne
C
C
D000328:Adult; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood; D001760:Bleeding Time; D001792:Blood Platelets / Q000201:enzymology*; D015232:Dinoprostone; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D011458:Prostaglandins E / Q000096:biosynthesis; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013927:Thrombosis / Q000517:prevention & control*; D013929:Thromboxane B2 / Q000096:biosynthesis; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D001095:Arachidonic Acids; D007093:Imidazoles; D011458:Prostaglandins E; C029166:dazoxiben; D016718:Arachidonic Acid; D013929:Thromboxane B2; C048180:1-(3-benzyloxy-1(E)octenyl)imidazole; D013930:Thromboxane-A Synthase; D015232:Dinoprostone