MECHANISM OF ANTI-PLATELET AGGREGATING ACTION OF DILAZEP

• Published in: Journal of Pharmacobio-Dynamics Vol. 8; no. 2; pp. 77 - 83
• Main Authors: TAKENAGA, MITSUKO, KITAGAWA, HARUO, HIRAI, AIZAN, TAMURA, YASUSHI, YOSHIDA, SHO
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.01.1985; Pharmaceutical Society of Japan
• Subjects: 12-lipoxygenase; Adenosine Diphosphate - pharmacology; Arachidonic Acid; Arachidonic Acids - metabolism; Azepines - pharmacology; Biological and medical sciences; Blood Platelets - metabolism; Blood. Blood coagulation. Reticuloendothelial system; Carbon Radioisotopes; Collagen - pharmacology; Dilazep - pharmacology; Epinephrine - pharmacology; Humans; In Vitro Techniques; Medical sciences; Nucleotides, Cyclic - blood; Pharmacology. Drug treatments; Platelet Aggregation - drug effects; Thromboxane B2 - biosynthesis; Platelet; Arachidonic acid; Mechanism of action; Biological activity; Antiplatelet agent; Arachidonic acid derivatives; Thromboxane A2; Prostaglandin synthase
• ISSN: 0386-846X; 1881-1353
• DOI: 10.1248/bpb1978.8.77

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 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 plateler membrane phospholipids and the reduced conversion of released AA to TXA2.