咪苯嗪酮对血小板聚集、血栓形成和血小板环磷酸腺苷含量的影响

本文观察了新型强心剂咪苯嗪酮(Cl-914)对血小板聚集、血栓形成和血小板cAMP含量的影响。用比浊法测定Cl-914体外抑制AA,ADP和胶原诱导兔血小板聚集的IC_(50),分别为2.6,8.9和15.8μM;大鼠iv Cl-914 1.25mg/kg能抑制实验性血栓形成,20 mg/kg能抑制上述三种诱导剂引起的血小板聚集。在体外,用竞争性蛋白结合法测定,CI-914可使洗涤兔血小板cAMP含量明显升高。CI-914能以剂量依赖方式协同PGE_1抑制血小板聚集和升高血小板cAMP的含量。提示CI-914升高血小板cAMP含量可能是其抑制血小板聚集和抗血栓形成的主要机理。

Effect of 4,5-dihydro-6-[4-(1H-imidazo1-1-y1)phenyl]-3(2H)-pyridazinone monohydrochloride (Cl-914) on platelet aggregation,thrombosis and cAMP level in platelets

Effects of a novel cardio-tonic.4,5-dihydro-6-4-(1H-imidazol-l-yl)phe-nyl]-3(2H)-pyridazinone monohydrochlo-ride (Cl-914)on platelet aggregation,thrombosis and cAMP level in platelets are reported.CI-914 inhibited platelet aggregation induced by arachidonic acid (AA),ADP and collagen in platelet rich plasma from rabbits in vitro,with IC50 values of 2.6,8.9 and 15.8μM respectively.In rats,CI-914 impeded all the above inducer-triggered platelet aggregation and experimental thrombosis after iv administration.CI-914 caused a dose-related increase in cAMP level in washed platelets from rabbits as measured by competitive protein-binding assay.Used incombination with an ade-nylate cyclase stimulator,prostaglandin E1,CI-914 was found to be significantly potentiated both in the inhibition on AA-induced platelet aggregation in vitro and in the increase of cAMP level in washed platelets.It is suggested that the main mechanism of inhibitory actions of CI-914 on platelet aggregation and thrombosis might be increasing the cAMP level in platelets.