De Clerck F, Van Nueten J M
Biochem Pharmacol. 1983 Mar 1;32(5):765-71. doi: 10.1016/0006-2952(83)90574-9.
Flunarizine, a calcium (Ca2+)-entry blocker, selective for vascular tissues, inhibits in a concn-dependent way the contraction of isolated rat caudal artery preparations induced by mediators derived from thrombin-stimulated rat platelets. This inhibition is slow in onset and is of prolonged duration. Specific measurements and pharmacological analysis show 5-hydroxytryptamine (5HT) and thromboxane A2 (TXA2) to be the main mediators involved. Comparison with exogenously added agonists shows amplification between 5HT and TXA2 at the level of the vascular smooth muscle cells. Combined treatment with ketanserin, a selective 5HT2 receptor antagonist, and suprofen, a fatty acid cyclo-oxygenase inhibitor, shows that flunarizine inhibits the 5HT-induced as well as the prostaglandin-induced components of the contraction. The compound does not affect the release of 5HT from the platelet and does not interfere with the biosynthesis of TXA2 from endogenous platelet arachidonic acid; it reduces the amounts of TXB2 and HHT and increases the production of HETE from exogenous [14C]arachidonic acid by washed rat platelets.
氟桂利嗪是一种对血管组织有选择性的钙（Ca2+）通道阻滞剂，它以浓度依赖性方式抑制由凝血酶刺激的大鼠血小板衍生的介质诱导的离体大鼠尾动脉标本的收缩。这种抑制起效缓慢且持续时间长。特定的测量和药理学分析表明，5-羟色胺（5HT）和血栓素A2（TXA2）是主要的参与介质。与外源性添加的激动剂比较表明，在血管平滑肌细胞水平上5HT和TXA2之间存在放大作用。用选择性5HT2受体拮抗剂酮色林和脂肪酸环氧化酶抑制剂舒洛芬联合治疗表明，氟桂利嗪抑制收缩中5HT诱导的成分以及前列腺素诱导的成分。该化合物不影响血小板释放5HT，也不干扰内源性血小板花生四烯酸合成TXA2；它减少了TXB2和HHT的量，并增加了经洗涤的大鼠血小板由外源性[14C]花生四烯酸产生的HETE的量。
