Ketanserin及其合成類似物對血小板凝集反應的影響

Effect of Ketanserin and its Analogues on Platelet Aggregation

周志中(Tz-Chong Chou)；陳基旺(Jin-Wang Chern)；丁予安(Yu-An Ding)

血小板凝集作用 ； Ketanserin ； ADP ； Platelet aggregation

Journal of Medical Sciences

10卷2期（1989 / 04 / 01）

87 - 92

繁體中文

Ketanserin是SerotoninS2接受器阻斷劑，具有降血壓及抑制血小板凝集作用，本研究是以正常健康者血液為檢體，以Ketanserin及其合成類似物，測試其對ADP誘導之血小板凝集反應的影響情形，以了解這些合成藥物是否比Ketanserin有更強的抑制效果。當藥物最終濃度為1.43×10^(-4) M，1.43×10^(-5) M，1.43×10^(-6) M，1.43×10^(-7) M時，Ketanserin其合成類似物如AL-079，AL-161，AL-091等對第一相凝集圖的凝集斜率（R1）及凝集高度（H1）值與控制組接近，無明顯抑制情形。而在第二相凝集圖中，上述所有藥最終濃度為1.43×10^(-4) M時，凝集斜率（R2）幾完全被抑制，而在凝集總高度（T1）值上，當藥物最終濃度為1.43×10^(-7) M時，四藥物的抑制不明顯且不具統計的明顯差異，但隨濃度增大，抑制現象逐漸加強，當濃度為1.43×10^(-4) M時，Ketanserin抑制40%，AL-079抑制37%，AL-161抑制35%，AL-091抑制52%，由上結果顯示Ketanserin及其合成類似物主要是抑制血小板第二相凝集反應，且隨劑量增加而抑制加強，一般來說，四種藥物抑制效果彼此相類似，惟AL-091號合成物較其它稍強。

Ketanserin is a highly selective S2-serotonergic antagonist that is widely used in the lowering of blood pressure and inhibition of platelet aggregation. The aim of this work is to study the effect of ketanserin and its analogues on ADP-induced platelet aggregation in normotensive healthy patients in order to determine wheter or not the inhibitory effects of the analogues are stronger than ketanserin. When katanserin, AL-079, AL-191 and AL-091's final concentration were 1.43×10^(-4) M, 1.43×10^(-5) M, 1.43×10^(-6) M and 1.43×10^(-7) M, the values of all agents aggregatory slope (R1) and height (H1) of primary aggregation are similar to the control, showing no significant inhibition. When final concentration of all agents was 1.43×10^(-4) M, the aggregatory slope (R2) of the secondary aggregation was almost completely inhibited. The agents maximal amplitude (HT) of platelet aggregations were not reduced obviously at 1.43×10^(-7) M, but at an increasing concentration, there is increasing inhibition of the maximal amplitude. The inhibitory percentage of HT at 1.43×10^(-4) M by ketanserin is 40%, AL-079 37%, AL-161 35%, and AL091 52% separately,. The results suggest ketanserin and its analogues mainly inhibited secondary platelet aggregation and has a doseresponse relationship. In short, the inhibitory effect of the four agents on platelet aggregation induced by ADP were similar, but the AL-091 compound was slightly stronger than the others.