Effects of nimodipine on platelet aggregation and the activity of enzymes in arachidonic acid metabolism.
The effects of nimodipine on platelet aggregation and arachidonic acid (AA) metabolism were studied in order to explore its effect on patients with thrombosis or cardiovascular disease. The results indicate that nimodipine (50-350 mumol/L) significantly inhibits platelet aggregation induced by ADP, AA, and ionophore A23187 in a dose dependent manner. The inhibitory effects induced by ionophore A23187 could be partially antagonized by calcium (1 mmol/L). When the substrate was AA and the enzyme was supplied by pig lung microsomes, nimodipine (50-400 mumol/L) significantly reduced the generation of TXB2 and 6-keto-PGF 1 a in parallel. When the substrate was prostaglandin endoperoxide, however, the levels of TXB2 and 6-keto-PGF 1 a were not significantly altered in the same concentration range. The results suggest that nimodipine is a cyclooxygenase inhibitor, and its ability to inhibit platelet aggregation is related to its calcium blocking effect.
Li
J
J
Institute of Basic Medical Sciences, CAMS, Beijing.
Wang
Z
Z
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D008861:Microsomes / Q000378:metabolism; D009553:Nimodipine / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D013552:Swine; D013929:Thromboxane B2 / Q000378:metabolism
D001095:Arachidonic Acids; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D013929:Thromboxane B2; D009553:Nimodipine; D015121:6-Ketoprostaglandin F1 alpha