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.
