The action of halofenate on platelet shape change and prostaglandin synthesis.
HAL, a congener of clofibrate, has previously been shown to inhibit epinephrine- and ADP-induced platelet aggregation and 14C-serotonin release. We further investigated the site of action of HAL by examining platelet shape change, MDA production as a measure of prostaglandin synthesis, and platelet aggregation and MDA production induced by SA. At the usual maximal therapeutic concentration of HAL (0.96 mM), this drug did not affect the velocity of platelet shape change as measured by a spectrophotometric method. However, at a higher concentration (3.12 mM), HAL significantly inhibited shape change (p less than 0.01). When epinephrine was used to initiate aggregation of PRP, HAL (0.96 mM) was found to inhibit MDA production over a wide range of epinephrine concentrations (p less than 0.01). This was not due to a direct inhibition of prostaglandin formation, since HAL had no effect on SA-induced platelet aggregation or MDA production. Aspirin (4 mM), on the other hand, produced a marked inhibition of MDA production and of platelet aggregation after stimulation with SA. We conclude that HAL works to inhibit some step in the platelet reaction prior to the appearance of free arachidonic acid.
D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D006016:Glycolates / Q000494:pharmacology*; D006218:Halofenate / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008315:Malondialdehyde / Q000378:metabolism; D008954:Models, Biological; D010974:Platelet Aggregation / Q000187:drug effects; D011453:Prostaglandins / Q000096:biosynthesis*
D006016:Glycolates; D011453:Prostaglandins; D008315:Malondialdehyde; D006218:Halofenate; D001241:Aspirin; D004837:Epinephrine