Meseclazone, 5-Chlorosalicylic Acid and Acetylsalicvlic Acid

Summary

Meseclazone and its major metabolite, 5-chlorosalicylic acid (5-CSA) have been shown to possess anti-inflammatory, analgesic and antipyretic activity. The comparative effects of these compounds on platelet aggregation were evaluated in vitro and ex vitro with acetylsalicylic acid (ASA). in vitro, meseclazone and ASA exhibited almost identical inhibitory potency of secondary phase ADP aggregation while 5-CSA was less effective. Moreover, collagen aggregation was inhibited by all three agents: ASA > meseclazone > 5- CSA. Thrombin-induced aggregation was inhibited to approximately the same extent by 5- CSA and ASA while meseclazone was inactive. The in vitro effects on the release-inducing aggregants were confirmed by ex vitro experiments in rats. These demonstrated that ASA and meseclazone inhibited collagen-induced aggregation 1 and 4 hr after oral administration although ASA was three to four times more active. ASA, but not meseclazone, was still effective 24 hr after administration. Bleeding times in rats 1 and 4 hr following oral administration of meseclazone and ASA were not altered. It is concluded that meseclazone and/or 5-CSA inhibit in vitro and ex vitro platelet aggregation initiated by the release reaction similar to ASA and other non-steroidal anti-inflammatory drugs.