Inhibition of platelet aggregation by a new agent, 2,2'-dithiobis-(N-2-hydroxypropyl benzamide) (KF4939).
KF4939, 2,2'-dithiobis-(N-2-hydroxypropylbenzamide), is a potent inhibitor of platelet aggregation in vitro in rabbit and human PRP. This agent inhibited both cyclooxygenase product-dependent (collagen and arachidonate) and independent (ADP and thrombin)-platelet aggregations. This action carried over to ex vivo situation following intraduodenal dosing as demonstrated in rabbits. KF4939 inhibited experimentally induced thrombocytopenias in rats and pulmonary thrombosis in mice following oral doses in a range of 25-300mg/kg. These results indicate that KF4939 is a new orally active inhibitor of platelet aggregation possessing a different mode of action from cyclooxygenase inhibition.
D000244:Adenosine Diphosphate / Q000009:adverse effects; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000009:adverse effects; D001241:Aspirin / Q000494:pharmacology; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology*; D003094:Collagen / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010208:Papaverine / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013917:Thrombin / Q000494:pharmacology; D013921:Thrombocytopenia / Q000139:chemically induced; D013927:Thrombosis / Q000139:chemically induced; D013928:Thromboxane A2 / Q000494:pharmacology
D001095:Arachidonic Acids; D001549:Benzamides; D005343:Fibrinolytic Agents; D016718:Arachidonic Acid; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; C037861:2,2'-dithiobis(N-2-hydroxypropylbenzamide); D003094:Collagen; D010208:Papaverine; D013917:Thrombin; D001241:Aspirin