Mechanism of anti-platelet aggregating action of dilazep.
In vitro effect of Dilazep on the release and metabolism of arachidonic acid (AA) in human platelets was studied. Dilazep reduced in a dose-dependent manner platelet aggregation and thromboxane B2 (TXB2) formation when stimulated by adenosine diphosphate, collagen and epinephrine. Dilazep decreased thrombin-induced release of [14C]arachidonic acid ([14C]AA) from platelets prelabeled with [14C]AA. The conversion of [14C]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 TXB2 formation by Dilazep may be ascribed to the impairment of AA release from platelet membrane phospholipids and the reduced conversion of released AA to TXA2.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001381:Azepines / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism; D002250:Carbon Radioisotopes; D003094:Collagen / Q000494:pharmacology; D004109:Dilazep / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009712:Nucleotides, Cyclic / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D013929:Thromboxane B2 / Q000096:biosynthesis
D001095:Arachidonic Acids; D001381:Azepines; D002250:Carbon Radioisotopes; D009712:Nucleotides, Cyclic; D016718:Arachidonic Acid; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D003094:Collagen; D004109:Dilazep; D004837:Epinephrine