title: The effects of TFC-612, a 7-THIA prostaglandin E1 derivative, on platelet function.
abstract: The anti-platelet activities of TFC-612, methyl 6-(( 1R,2S,3R)-3-hydroxy-2-((1E,3S,5R)-3-hydroxy-5-methyl-1-nonenyl)-5- oxocyclopentyl) thio)hexanoate, were compared to prostaglandin E1 (PGE1). TFC-612 inhibited human, guinea-pig and rabbit platelet aggregation induced by ADP, collagen or epinephrine with potency 1-8 times that of PGE1. TFC-612 also inhibited thrombin induced (14C) serotonin release in rabbit platelets. Platelet aggregation was dose dependently inhibited 1 hr after oral administration of TFC-612 (0.32-1.0 mg/kg) and the inhibition lasted up to 6 and 24 hours at 0.32 and 1.0 mg/kg, respectively, in guinea-pigs. In contrast, PGE1 had no effect with oral administration at a dose of 3.2 mg/kg. TFC-612 (0.32-3.2 micrograms/kg, iv) induced platelet disaggregation of thrombi on Achilles tendon in the extracorporeal shunt model in cats. In addition, TFC-612 (1 mg/kg, po) inhibited the adhesiveness of guinea-pig platelets to a glass bead column ex vivo. TFC-612 increased cyclic AMP (cAMP) levels in rabbit platelets. Thus, the anti-platelet action of TFC-612 may be due to an increase in cAMP levels. These results indicate that TFC-612 might be an orally active anti-thrombotic drug.
authors.affiliation: Research Laboratories, Fujisawa Pharmaceutical Co., Ltd, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Motoyama
authors.forename: Y
authors.initials: Y
authors.lastname: Sakata
authors.forename: J
authors.initials: J
authors.lastname: Seki
authors.forename: T
authors.initials: T
authors.lastname: Asada
authors.forename: Y
authors.initials: Y
authors.lastname: Namikawa
authors.forename: H
authors.initials: H
authors.lastname: Horiai
authors.forename: T
authors.initials: T
authors.lastname: Ono
mesh_terms: D000284:Administration, Oral; D000527:Alprostadil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000097:blood; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000097:blood / Q000378:metabolism
chemical_list: D010975:Platelet Aggregation Inhibitors; D012701:Serotonin; C054546:TFC 612; D000242:Cyclic AMP; D000527:Alprostadil