Teng C M, Hsueh C M, Chang Y L, Ko F N, Lee S S, Liu K C
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan.
J Pharm Pharmacol. 1997 Jul;49(7):706-11. doi: 10.1111/j.2042-7158.1997.tb06096.x.
Two aporphines (boldine and laurolitsine) and five phenanthrene alkaloids (litebamine, secoboldine, N-cyanosecoboldine, N-methylsecoglaucine and N-methylsecopredicentrine) were evaluated in-vitro for their ability to inhibit platelet aggregation. All seven alkaloids inhibited aggregation of rabbit platelets and inhibited the release of ATP induced by arachidonic acid and collagen in rabbit platelets. Those aggregations induced by platelet-activating factor (PAF), thrombin, U46619 and ADP were inhibited by the three N-substituted secoboldine derivatives only. Thromboxane B2 formation caused by arachidonic acid was also suppressed by these compounds. They did not affect the generation of [3H]inositol monophosphate caused by collagen, PAF and thrombin in the presence of indomethacin. Platelet cyclic AMP level was unaffected by litebamine, but was increased by N-methylsecoglaucine. Litebamine suppressed the secondary aggregation, but not the primary aggregation, induced by ADP and adrenaline in platelet-rich plasma from man, whereas N-methylsecoglaucine inhibited both primary and secondary aggregation. It is concluded that the antiplatelet effect of these seven aporphine and phenanthrene alkaloids is mainly a result of inhibition of thromboxane A2 formation; N-methylsecoglaucine has additional antiplatelet activity as a result of increasing the levels of platelet cyclic AMP.
对两种阿朴啡碱（去甲异波尔定和月桂番荔枝碱）和五种菲生物碱（光千金藤碱、去甲异波尔定、N-氰基去甲异波尔定、N-甲基去甲塞考劳辛和N-甲基去甲前胡素）进行了体外实验，评估它们抑制血小板聚集的能力。所有七种生物碱均抑制兔血小板聚集，并抑制花生四烯酸和胶原蛋白诱导的兔血小板中ATP的释放。只有三种N-取代的去甲异波尔定衍生物抑制由血小板活化因子（PAF）、凝血酶、U46619和ADP诱导的聚集。这些化合物还抑制了花生四烯酸引起的血栓素B2的形成。在吲哚美辛存在的情况下，它们不影响胶原蛋白、PAF和凝血酶引起的[3H]肌醇单磷酸的生成。血小板环磷酸腺苷水平不受光千金藤碱影响，但N-甲基去甲塞考劳辛可使其升高。光千金藤碱抑制人富血小板血浆中由ADP和肾上腺素诱导的继发性聚集，但不抑制原发性聚集，而N-甲基去甲塞考劳辛则抑制原发性和继发性聚集。结论是，这七种阿朴啡碱和菲生物碱的抗血小板作用主要是抑制血栓素A2形成的结果；N-甲基去甲塞考劳辛由于提高了血小板环磷酸腺苷水平而具有额外的抗血小板活性。
