Characterization of imidazo[1,5-a]pyridine-5-hexanoic acid (CGS 13080) as a selective thromboxane synthetase inhibitor using in vitro and in vivo biochemical models.
CGS 13080 inhibited cell-free thromboxane synthetase with an IC50 of 3 nM. It was at least five orders of magnitude less potent toward other key enzymes involved in arachidonic acid metabolism. Submicromolar concentrations inhibited calcium ionophore-induced formation of thromboxane B2 by intact human platelets with concomitant accumulation of prostaglandin E2. Oral doses lower than 1 mg/kg in rats suppressed the elevations of plasma thromboxane B2 induced by calcium ionophore. This was attended by shunting of endoperoxide substrate to 6-keto-prostaglandin F1 alpha and prostaglandin E2. CGS 13080 is one of the most potent and selective thromboxane synthetase inhibitors yet identified.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011458:Prostaglandins E / Q000097:blood; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D011458:Prostaglandins E; D011725:Pyridines; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C037787:pirmagrel; D010088:Oxidoreductases; D013930:Thromboxane-A Synthase