Berrettini M, De Cunto M, Parise P, Grasselli S, Nenci G G
Institute of Semeiotica Medica, University of Perugia, Italy.
Eur J Clin Pharmacol. 1990;39(5):495-500. doi: 10.1007/BF00280943.
Picotamide (G 137), a new non prostanoid inhibitor of in vitro arachidonic acid induced platelet aggregation, has been further characterized in in vitro and ex vivo studies. When whole blood was activated with collagen in the presence of picotamide 5 x 10(-4) M, thromboxane B2 production was decreased, and 6-keto-PGF1 alpha generation was significantly increased, suggesting a reorientation of platelet endoperoxide metabolism following blockade of thromboxane synthetase. Picotamide also inhibited platelet aggregation and clot retraction induced by the endoperoxide analogue U46619 in human platelets, indicating thromboxane A2-receptor antagonism, possibly of competitive nature. A single oral dose of picotamide 1 g in 24 healthy volunteers produced a significant inhibition of collagen, arachidonic acid and U46619-induced platelet aggregation. Serum levels of thromboxane B2 were also reduced. Chronic administration of picotamide 1.2 g/d to patients with vascular disease resulted in a prompt and persistent fall in their increased plasma levels of beta-thromboglobulin. The results indicate that picotamide is a combined thromboxane B2-synthetase inhibitor and thromboxane A2-receptor antagonist in human platelets, and that it may prove useful as an antithrombotic agent.
匹可托胺（G 137）是一种新型非前列腺素类体外花生四烯酸诱导血小板聚集的抑制剂，已在体外和体内研究中得到进一步表征。当在5×10⁻⁴M匹可托胺存在下用胶原激活全血时，血栓素B2的产生减少，而6-酮-前列腺素F1α的生成显著增加，这表明在血栓素合成酶被阻断后血小板内过氧化物代谢发生了重新定向。匹可托胺还抑制人血小板中内过氧化物类似物U46619诱导的血小板聚集和血块收缩，表明具有血栓素A2受体拮抗作用，可能是竞争性的。24名健康志愿者单次口服1g匹可托胺可显著抑制胶原、花生四烯酸和U46619诱导的血小板聚集。血栓素B2的血清水平也降低。对血管疾病患者长期给予1.2g/d匹可托胺可使其升高的血浆β-血小板球蛋白水平迅速且持续下降。结果表明，匹可托胺是一种人血小板中血栓素B2合成酶抑制剂和血栓素A2受体拮抗剂的组合，可能作为一种抗血栓药物有用。
