Mepacrine, in addition to its established antilipolytic activity, was also found to
inhibit the conversion of 14C-arachidonic acid to 14C-thromboxane B2 in human washed platelets. In the concentration range of 3.33-33 μM, mepacrine exerted
a dose dependent inhibition of arachidonate conversion to thromboxane B2 in parallel to inhibition of arachidonate-induced platelet aggregation. Mepacrine
inhibition of thromboxane formation was not accompanied by a concomitant increase
in other cyclooxygenase products. Furthermore, mepacrine did not affect platelet transformation
of added prostaglandin H2 to thromboxane A2 and other products. These results indicate that mepacrine inhibits the cyclooxygenase
enzyme and not thromboxane synthase. In washed platelets, mepacrine inhibition of
arachidonic acid conversion to thromboxane A2 appears to be a major factor in the overall inhibitory effect of the compound on
the combined process of arachidonate release from cellular phospholipids and its conversion
to proaggregatory products.
Keywords
Mepacrine - Platelet aggregation - Arachidonic add - Cyclooxygenase
