抗凝藥：血小板環腺苷酸磷酸二酯酶及前列凝素A2合成酶抑制劑

Anti-aggregation Agents: Inhibitors of Platelet cAMP Phosphodiesterase and TXA2 Synthase

李安榮(An-Rong Lee) ； 林潼亮(Tung-Lung Lin) ； 李小鳳(Hsiao-Feng Lee) ； 黃文鑫(Wen-Hsin Huang)

《Journal of Medical Sciences》 13卷1期 (1992/08) Pp. 1-16

摘要

血小板活化凝集易形成血栓及栓塞，並為造成心絞痛、心肌梗塞及中風的原因。活化之血小板促使快速形成凝血酶，後者又會強力活化循環之血小板，致使反復刺激血小板凝集，形成血栓或導致動脈粥樣硬化。凝血酶同時促使纖維蛋白原轉換成纖維蛋白，經聚合橫向連結後，能安定所形成的血小板簇。血小板凝集分為花生四烯酸依賴型與非依賴型兩種，故抗凝藥亦分成二種，前者計有環氧化酶抑制劑、TXA2合成酶抑制劑、TXA2拮抗劑、PGI2活化劑等；後者包括cAMP PDE抑制劑及腺苷酸磷酸二酯酶活化劑等。本文回顧近十年來，有關於cAMP PDE、TXA2合成酶抑制劑，及其合併抑制劑之文獻，並對其化學結構與活性作系統性介紹，以提供從事心血管藥物研究之參考。

關鍵字

凝集 ； 血小板 ； 環腺苷酸磷酸二酯酶 ； 前列凝素A2合成酶

並列摘要

Platelet activation is a complex phenomenon, which causes platelet aggregation and plays an important role in occlusive thrombus formation at the site of adhesion and downstream after embolization. Both are implicated as the early events in the genesis of angina, myocardial infarction and stroke. Thrombin, formed in the course of coagulation cascade, initiates platelet activation and subsequently induces platelet aggregation and release of ADP from various storage granules of platelets. Thrombin also promotes the conversion of fibrinogen to fibrin, which polymerizes, cross-linked and stabilizes the platelet aggregation. ADP released from granules can also activate platelets, leading to activation of additional platelets. Platelet aggregation can be occurred as arachidonic acid (AA)-dependent and AA-independent mechanisms, and compounds possessing anti-aggregating activity are categorized accordingly. A general rule appears to be that drugs which cause an increase in intracellular cAMP inhibit platelet aggregation whereas agents resulting in a reduction in cAMP levels accelerate platelet aggregation. This review article will focus on inhibitors of platelet cAMP phosphodiesterase and those of thromboxane A2 synthase, with emphasis on newer, more potent compounds as potential anti-thrombotic drugs.

並列關鍵字

Aggregation ； Platelet ； cAMP phosphodiesterase ； Thromboxane A2 synthase