title: Effects of ONO-3708, an antagonist of the thromboxane A2/prostaglandin endoperoxide receptor, on platelet aggregation and thrombosis.
abstract: The beneficial effects of an antagonist of the thromboxane A2/prostaglandin endoperoxide receptor, 7-[2 alpha,4 alpha-(dimethylmethano)-6 beta-(2-cyclopentyl-2 beta- hydroxyacetamido)-1 alpha-cyclohexyl]-5(Z)-heptenoic acid (ONO-3708) on thrombosis were examined. ONO-3708 at 0.1-3 microM inhibited the human platelet aggregation induced by thromboxane A2, prostaglandin H2, collagen, ADP (secondary phase) and epinephrine (secondary phase) without affecting prostanoid synthesis and the content of cyclic AMP in platelets. The in vivo effects, on coronary thrombosis in this case, were examined in two canine models. ONO-3708, 3 to 300 micrograms/kg i.v., prevented dose dependently the coronary thrombosis induced by partial obstruction of the coronary artery. ONO-3708, 3 micrograms/kg per min i.v., significantly prevented electrically stimulated coronary thrombosis without affecting systemic blood pressure and heart rate. These results indicate that the thromboxane A2/prostaglandin endoperoxide receptor could play an important role in the pathogenesis of thrombosis and that ONO-3708 may have therapeutic advantages in preventing thrombosis.
authors.affiliation: Minase Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kondo
authors.forename: R
authors.initials: R
authors.lastname: Seo
authors.forename: M
authors.initials: M
authors.lastname: Naka
authors.forename: T
authors.initials: T
authors.lastname: Kitagawa
authors.forename: K
authors.initials: K
authors.lastname: Wakitani
authors.forename: M
authors.initials: M
authors.lastname: Sakata
authors.forename: H
authors.initials: H
authors.lastname: Kira
authors.forename: T
authors.initials: T
authors.lastname: Okegawa
authors.forename: A
authors.initials: A
authors.lastname: Kawasaki
mesh_terms: D000818:Animals; D003094:Collagen / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000502:physiology; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D005343:Fibrinolytic Agents; D066298:In Vitro Techniques; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000187:drug effects*; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013997:Time Factors
chemical_list: D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D011982:Receptors, Prostaglandin; D013928:Thromboxane A2; C049855:ONO 3708; D003094:Collagen