Egawa M, Nakajima I, Misu Y
Jpn J Pharmacol. 1982 Apr;32(2):273-81. doi: 10.1254/jjp.32.273.
Effects of cerebral vasodilators such as bencyclane, cinnarizine, and papaverine were comparatively studied using helically cut basilar and superior mesenteric arteries and radial muscle preparations of pulmonary arteries with the sympathetic nerve isolated from rabbits. The order of relaxation activities on high K+-induced contractures was cinnarizine>bencyclane>papaverine in basilar strips and cinnarizine>papaverine>bencyclane in mesenteric strips. Relaxation responses of basilar strips to cinnarizine and bencyclane were faster and more marked than those seen in mesenteric strips. Responses to papaverine were equipotent in both preparations. The action of cinnarizine alone was irreversible. In mesenteric strips, the order of the sensitivity of contractile responses to cumulatively applied biogenic amines was serotonin>noradrenaline>histamine. Cinnarizine produced an antihistaminergic action, while bencyclane produced an antiserotonergic action. In pulmonary arteries, 6 x 10(-6) g/ml papaverine inhibited contractile responses to 2, 5, and 25 Hz nerve stimulation in a frequency-independent manner together with inhibition of responses to noradrenaline. Bencyclane at 6 x 10(-6) and 10(-5) g/ml selectively inhibited in a dose-dependent manner contractile responses only to 25 Hz without inhibition of responses to noradrenaline. These results were discussed in comparison with findings of the cerebral vasodilators obtained using other experimental techniques. Spiral strips of basilar arteries from rabbits in combination with peripheral arteries may be used as a simple quantitative, and reproducible screening method in a preclinical stage for drug evaluation of cerebral vasodilators.
使用从兔分离出交感神经的螺旋形切割的基底动脉、肠系膜上动脉以及肺动脉的环行肌制备物,比较研究了苄环烷、桂利嗪和罂粟碱等脑血管扩张剂的作用。在高钾诱导的收缩方面,舒张活性顺序在基底动脉条中为桂利嗪>苄环烷>罂粟碱,在肠系膜动脉条中为桂利嗪>罂粟碱>苄环烷。基底动脉条对桂利嗪和苄环烷的舒张反应比肠系膜动脉条更快且更明显。两种制备物中对罂粟碱的反应相同。单独使用桂利嗪的作用是不可逆的。在肠系膜动脉条中,对累积应用的生物胺的收缩反应敏感性顺序为5-羟色胺>去甲肾上腺素>组胺。桂利嗪产生抗组胺作用,而苄环烷产生抗5-羟色胺作用。在肺动脉中,6×10⁻⁶g/ml罂粟碱以频率非依赖性方式抑制对2、5和25Hz神经刺激的收缩反应以及对去甲肾上腺素的反应。6×10⁻⁶和10⁻⁵g/ml的苄环烷仅以剂量依赖性方式选择性抑制对25Hz的收缩反应,而不抑制对去甲肾上腺素的反应。结合其他实验技术获得的脑血管扩张剂的研究结果对这些结果进行了讨论。兔基底动脉螺旋条与外周动脉相结合可作为一种简单的定量且可重复的筛选方法,用于脑血管扩张剂药物评价的临床前阶段。