Akashi A, Hirohashi M, Suzuki I, Shibamura S, Kasahara A
Nihon Yakurigaku Zasshi. 1979 Jul;75(5):507-16. doi: 10.1254/fpj.75.507.
Cardiovascular effects of cinepazide were compared with those of cinnarizine and papaverine. Cinepazide (3-30 mg/kg, i.v.) produced a dose-related and transient increase in vertebral, carotid, renal and femoral arterial flow as well as cardiac output and a decrease in total peripheral resistance in anesthetized dogs. The magnitude and duration of mesenteric vasodilatation induced by cinepazide was much greater as compared to other vascular effects, and these effects were associated with a prolonged hypotension. The drug exerted positive inotropic and chronotropic actions, the latter being followed by bradycardia with the highest dose. Cinnarizine (0.3-3 mg/kg, i.v.) produced a greater increase in vertebral blood flow with bradycardia and papaverine (0.1-1 mg/kg, i.v.) produced a remarkable carotid vasodilatation with cardiac stimulation. Both reference drugs decreased renal blood flow. Cinepazide (30 mg/kg, i.v.) potentiated the vertebral vasodilator response of dogs to intravertebral adenosine and cyclic AMP, while cinnarizine (3 mg/kg i.v.) reduced their vasodilator effects. Intravertebral cinepazide(1-10 mg), like cinnarizine (0.1-1 mg) and papaverine (0.1-1 mg), increased vertebral blood flow in a dose-related manner and the effect was partially inhibited by intravenous pretreatment with aminophylline but not by pretreatment with autonomic antagonists. These antagonists did not modify the cinnarizine effect. Cinepazide resembled cinnarizine and papaverine in that the drug antagonized rabbit aortic contraction induced by KCl, norepinephrine or CaCl2.
将桂哌齐特的心血管效应与桂利嗪和罂粟碱的心血管效应进行了比较。在麻醉犬中,静脉注射桂哌齐特(3 - 30mg/kg)可使椎动脉、颈动脉、肾动脉和股动脉血流以及心输出量呈剂量依赖性短暂增加,总外周阻力降低。与其他血管效应相比,桂哌齐特诱导的肠系膜血管舒张的程度和持续时间要大得多,且这些效应与持续性低血压相关。该药物具有正性肌力和变时作用,高剂量时变时作用后会出现心动过缓。静脉注射桂利嗪(0.3 - 3mg/kg)可使椎动脉血流增加且伴有心动过缓,静脉注射罂粟碱(0.1 - 1mg/kg)可使颈动脉显著舒张且伴有心脏兴奋。两种参比药物均使肾血流量减少。静脉注射桂哌齐特(30mg/kg)可增强犬对椎体内腺苷和环磷腺苷的血管舒张反应,而静脉注射桂利嗪(3mg/kg)则降低其血管舒张作用。椎体内注射桂哌齐特(1 - 10mg),与桂利嗪(0.1 - 1mg)和罂粟碱(0.1 - 1mg)一样,可使椎动脉血流呈剂量依赖性增加,且该效应可被静脉注射氨茶碱预处理部分抑制,但不能被自主神经拮抗剂预处理抑制。这些拮抗剂并未改变桂利嗪的作用。桂哌齐特与桂利嗪和罂粟碱类似,该药物可拮抗由氯化钾、去甲肾上腺素或氯化钙诱导的兔主动脉收缩。