Verapamil decreases the formation of thromboxane from exogenous 14C-arachidonic acid in human platelets in vitro.
The effects of verapamil on the metabolism of exogenous 14C-arachidonic acid were studied in human platelets in vitro. 1 mM verapamil decreased the formation of TXB2 and HHT and increased that of PGE2, PGD2 and PGF2 alpha. The radioactivity at the area of 12-HPETE on the thin layer chromatography plate was also increased by 1 mM verapamil. In addition, 10 microM and 1 mM verapamil caused a slight decreasing trend in the amount of free unmetabolized arachidonic acid. The results suggest that high concentrations of verapamil may decrease the formation of the aggregatory thromboxane and increase that of anti-aggregatory compounds, i.e. PGD2 and 12-HPETE in human platelets in vitro. However, as lower concentrations of verapamil (10 and 100 microM) had no significant effect on the metabolism of exogenous arachidonic acid, the anti-platelet effects of the drug at therapeutic concentrations are more likely to be mediated via other mechanisms, possibly via the inhibition of arachidonate release from the platelet membrane phospholipids.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood* / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D013929:Thromboxane B2 / Q000096:biosynthesis; D014700:Verapamil / Q000494:pharmacology*
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D013929:Thromboxane B2; D014700:Verapamil