De Clerck F, Xhonneux B, Tollenaere J P, Janssen P A
Thromb Res. 1985 Dec 1;40(5):581-96. doi: 10.1016/0049-3848(85)90297-x.
The potency for the inhibition of 5-hydroxytryptamine (5-HT)-induced human platelet aggregation by ketanserin, pipamperone, spiperone, cyproheptadine and BW 501 in vitro decreased as the reaction pH increased progressively from 7.4 to 8.6, the largest shift (X 1125) in IC50 value (pH 7.4: 4 X 10(-9) M; pH 8.6: 4.5 X 10(-6) M) being found for ketanserin. With such an alkaline pH-shift, the fraction of the ionized form of the drugs decreased, reduction of the inhibitory capacity and of the ionized fraction being strongly correlated. Ketanserin (40 mg orally, - 15 h) in human volunteers, completely inhibited the 5-HT-induced platelet aggregation measured ex vivo, when tested at a reaction pH of 7.4; without gassing with CO2 5% -O2 95%, the plasma pH became alkaline and the inhibitory potency of the drug was strongly reduced (-60%). This study demonstrates the importance of the reaction pH for the aggregation of human platelets induced by 5-HT and its inhibition by ketanserin.
在体外，随着反应pH值从7.4逐渐升高至8.6，酮色林、匹泮哌隆、螺哌隆、赛庚啶和BW 501对5-羟色胺（5-HT）诱导的人血小板聚集的抑制效力降低，酮色林的IC50值变化最大（相差1125倍，pH 7.4时为4×10⁻⁹ M；pH 8.6时为4.5×10⁻⁶ M）。随着pH值向碱性偏移，药物的离子化形式比例降低，抑制能力的降低与离子化比例的降低密切相关。在人类志愿者中，当在反应pH值为7.4时进行测试，口服40 mg酮色林（-15小时）可完全抑制离体测量的5-HT诱导的血小板聚集；在不通入5% CO₂-95% O₂的情况下，血浆pH值变为碱性，药物的抑制效力大幅降低（-60%）。本研究证明了反应pH值对于5-HT诱导的人血小板聚集及其被酮色林抑制的重要性。
