Chan W P, Levy J V
Department of Physiology and Pharmacology, University of the Pacific, San Francisco, CA 94115.
Prostaglandins. 1991 Oct;42(4):337-42. doi: 10.1016/0090-6980(91)90082-q.
Impedance aggregometry was used to evaluate the potency of anti-platelet agents on Platelet Activating Factor (PAF)--induced platelet aggregation in citrated human whole blood. Drugs were tested for ability to inhibit maximum aggregation to PAF. Dose response curves were obtained and the concentration of drug producing 50% inhibition of maximum aggregation (ED50) determined. ED50's (microM) for specific PAF antagonists WEB 2086, Ro 19-3704, FR-900452, BN 52021, L-652,731, CV 3988, WEB 2118 and 48740 RP are: 0.39, 2.4, 4.7, 19.5, 21.0, 5.32, 161.0, 924.0, respectively. ED50's for non-specific PAF antagonists, diltiazem, propranolol, ketotifen, procaine HCL, and lidocaine HCL are: 38.0, 56.0, 250.0, 513.0 and 768.0, respectively. Ibuprofen was inactive at 2300 microM. Results are consistent with concept that there are specific receptors on platelets mediating PAF-induced aggregation in whole blood. Aggregation is inhibited potently by specific and competitive PAF receptor antagonists. Whole blood aggregometry may be a valid method for predicting in vivo activity of PAF antagonists.
采用阻抗聚集法评估抗血小板药物对枸橼酸化人全血中血小板活化因子（PAF）诱导的血小板聚集的作用强度。检测药物抑制PAF最大聚集的能力。获得剂量反应曲线，并确定产生最大聚集50%抑制作用（ED50）的药物浓度。特异性PAF拮抗剂WEB 2086、Ro 19 - 3704、FR - 900452、BN 52021、L - 652,731、CV 3988、WEB 2118和48740 RP的ED50（微摩尔）分别为：0.39、2.4、4.7、19.5、21.0、5.32、161.0、924.0。非特异性PAF拮抗剂地尔硫䓬、普萘洛尔、酮替芬、盐酸普鲁卡因和盐酸利多卡因的ED50分别为：38.0、56.0、250.0、513.0和768.0。布洛芬在2300微摩尔时无活性。结果与全血中存在介导PAF诱导聚集的血小板特异性受体这一概念一致。特异性和竞争性PAF受体拮抗剂可有效抑制聚集。全血聚集法可能是预测PAF拮抗剂体内活性的有效方法。
