MECHANISM OF ANTI-PLATELET AGGREGATING ACTION OF DILAZEP

概要

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In vitro effect of Dilazep on the release and metabolism of arachidonic acid (AA) in human platelets was studied. Dilazep reduced in dose-dependent manner platelet aggregation and thromboxane B_2 (TXB_2) formation when stimulated by adenosine diphosphate, collagen and epinephrine. Dilazep decreased thrombin-induced release of [^<14>C]arachidonic acid ([^<14>C]AA) from platelets prelabeled with [^<14>C]AA. The conversion of [^<14>C]AA to cyclooxygenase metabolites was reduced by the addition of Dilazep, while that to 12-lipoxygenase metabolite was rather increased. Adenosine 3', 5'-cyclic monophosphate and guanosine 3', 5'-cyclic monophosphate levels in washed human platelets were not affected by the addition of Dilazep. These results suggest that the decreased TXB_2 formation by Dilazep may be ascribed to the impairment of AA release from plateler membrane phospholipids and the reduced conversion of released AA to TXA_2.
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