胍乙哌啶甲基衍生物的药理作用

小白鼠腹腔注射胍乙哌啶、BD-37、BD-38、胍乙啶和BD-31的LD₅₀分别为367,243,202,155和78 mg/kg。麻醉大白鼠和猫静脉注射胍乙啶、胍乙哌啶和BD-37出现血压短暂下降继而升压,然后再下降,而BD-38和BD-31仅有降压作用。急性降压强度BD-38和BD-31较强,BD-37和胍乙啶次之,胍乙哌啶最弱。胍乙啶、胍乙哌啶、BD-37和BD-31抑制酪胺的升压作用;对去甲肾上腺素的升压,除BD-31稍有抑制外,胍乙啶、BD-37和BD-38反有增敏作用。胍乙啶、胍乙哌啶和BD-37明显增强豚鼠心房的收缩,BD-38和BD-31则无此作用。离体豚鼠输精管和猫颈交感神经实验说明,BD-31阻断交感神经节的作用较强,对神经末梢也稍有阻断;BD-37和BD-38阻断交感神经末梢与胍乙啶的作用强度相仿;胍乙哌啶只对输精管稍有阻断作用。胍乙啶、胍乙哌啶、BD-37和BD-38可减低大鼠心脏内去甲肾上腺素的含量,BD-31未见减低。以上结果表明:BD-38能选择地阻断交感神经末梢,而无胍乙啶的交感类似反应,并具有较强的降压效果。

SOME PHARMACOLOGICAL ACTIONS OF METHYL- SUBSTITUTED PIPERIDINO ETHYLGUANIDINES

Three derivatives of piperidino ethyl guanidine sulphate (P) were synthesized by Bai et al in our Instituter: β-N-(2,2,6,6-tetramethylpiperidino)-ethyl-guanidine sulphate (BD-31), β-N-(2-methylpiperidino)-ethyl-guanidine sulphate (BD-37), and β-N-(cis-2,6-dimethylpiperidino)-ethyl-guanidine sulphate (BD-38). Their pharmacological actions were compared with guanethidine sulphate (G).The acute intraperitoneal LD₅₀ in mice of P, BD-37, BD-38, G and BD-31 were 367, 243, 202, 155 and 78 mg/kg, respectively. Intravenous injections of P, BD-37 and G in anaesthetized rats and cats brought about a transient lowering of blood pressure, followed by a rise and then a gradual decline, whereas BD-31 and BD-38 produced only a hypotension. For the hypotensive potency: BD-38 and BD-31>BD-37 and G>P. P, BD-37, BD-31 and G inhibited the hypertensive effect of tyramine. BD-37, BD-38 and G sensitized, but BD-31 inhibited slightly, the hypertensive effect of noradrenaline. P, BD-37 and G markedly augmented the contraction of guinea pig auricles, though BD-31 and BD-38 were devoid of this action. Experiments on cat sympathetic nerve and isolated guinea pig vas deferens showed that BD-31 blocked moderately the Sympathetic ganglion and blocked mildly the sympathetic nerve endings; BD-37 and BD-38 blocked sympathetic nerve endings to an extent simiiar to hatby G; P blocked slightly only the vas deferens preparation. P, BD-37, BD-38 and G decreased, but BD-31 did not decrease, the noradrenaline contents in the rat heart.En résumé: BD-38 selectively blocked the sympathetic nerve endings, lacked the sympathomimetic action of G, and possessed a considerable hypotensive action.