Ohnishi H, Yamaguchi K, Satoh M, Obata M, Uemura A, Toyonaka Y, Suzuki Y
Arzneimittelforschung. 1981;31(9):1425-9.
Pharmacological properties of 2-[(5-chloro-2-methoxyphenyl)azo]-1H-imidazole (M6434) were investigated in vivo and in vitro experiments. M6434 showed a dose-dependent pressor effect in conscious rats at oral doses ranging from 1 to 5 mg/kg. The pressor effect of M6434 was 10 times as potent as those of phenylephrine and methoxamine. M6434 also showed a dose-dependent pressor effect in anesthetized dogs at i.v. doses ranging from 3 to 30 micrograms/kg. The effect of M6434 returned to control level 30 to 45 min after i.v. injection. M6434 caused a contraction of isolated guinea-pig aortic spiral strip at concentrations ranging from 10(-8) to 10(-4) mol/l. pD2 value of M6434 was larger than those of the other sympathomimetics, yet the maximal response of M6434 was 83.4% of the maximal response of noradrenaline. Pretreatment with phentolamine caused a parallel shift of the concentration-response curve of M6434 to the right. However, this effect of M6434 on an isolated aorta was not diminished even in reserpinized guinea-pigs. Therefore, the pressor effect of M6434 may be due to the direct adrenergic alpha-stimulation. M6434 is expected to be effective for the oral treatment of hypotensive disorders.
在体内和体外实验中研究了2-[(5-氯-2-甲氧基苯基)偶氮]-1H-咪唑（M6434）的药理特性。M6434在清醒大鼠中口服剂量为1至5mg/kg时显示出剂量依赖性升压作用。M6434的升压作用比去氧肾上腺素和甲氧明强10倍。M6434在麻醉犬中静脉注射剂量为3至30μg/kg时也显示出剂量依赖性升压作用。静脉注射后30至45分钟，M6434的作用恢复到对照水平。M6434在浓度范围为10^(-8)至10^(-4)mol/L时可引起离体豚鼠主动脉螺旋条收缩。M6434的pD2值大于其他拟交感神经药，但M6434的最大反应是去甲肾上腺素最大反应的83.4%。用酚妥拉明预处理导致M6434的浓度-反应曲线平行右移。然而，即使在利血平化的豚鼠中，M6434对离体主动脉的这种作用也没有减弱。因此，M6434的升压作用可能是由于直接的肾上腺素能α刺激。M6434有望用于口服治疗低血压症。
