Effect of TEI-2117, a new antithrombotic agent: A fundamental study on platelet aggregation

Abstract

TEI-2117 (I), 2-(3-benzoyl-2, 5-dimethylpyrrole) propanol, is a novel compound synthesized by our laboratories. The effect of I was studied on human platelet aggregation and on prostaglandin biosynthesis in vitro comparing with indomethacin (IM). The compound (I) was more potent inhibitor than IM in arachidonic acid-induced platelet aggregation. I had similar inhibitory activity to that of IM in aggregation by collagen. It also inhibited the secondary phase of aggregation induced by epinephrine. Inhibition of the release of rabbit aorta contracting substances was also observed by preincubation of PRP with I. However, I was less active in inhibition of prostaglandin E2 formation when bovine seminale vesicles were used as an enzyme source. In the study of prostaglandin biosynthesis using human platelet microsome and 14C-arachidonic acid, the regulatory pattern of prostaglandin biosynthesis by I was different from that by IM. The effect of I on platelet aggregation was further studied in extra vivo. When I was administered subcutaneously (10mg/kg) or orally (100mg/kg) to guinea pig, 98 percent and 70 percent inhibition of platelet aggregation induced by arachidonic acid, was observed, whereas aspirin was nearly equipotent to I at the same dose. These result suggest that I may play in vivo effect on prevention of thrombus formation through antagonizing arachidonic acid metabolism in platelets.