肾上腺素能神经阻滞剂二甲基哌啶乙胍的药理
PHARMACOLOGY OF THE ADRENERGIC BLOCKING AGENT DIMETHYLPIPERIDINO ETHYL GUANIDINE
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摘要: 麻醉猫静注二甲基哌啶乙胍(BD-38)1~5mg/kg或十二指肠内注入10mg/kg,麻醉狗静注5mg/kg,均引起血压显著下降,心电图无明显的改变。BD-38部分抑制电刺激离体豚鼠回肠壁的收缩;显著地阻断电刺激动脉周围神经引起的回肠抑制性(松弛)反应。BD-38可明显地抑制电刺激猫内脏神经离中端所引起的升压。清醒猫静脉注射胍乙啶和BD-38(5或10mg/kg)引起瞬膜松弛的作用强度相同。清醒猫灌胃给胍乙啶和BD-38(10mg/kg),胍乙啶的瞬膜松弛作用强度只有BD-38的一半,增加剂量至20mg/kg,才达到BD-38组的松弛程度,说明BD-38胃肠道吸收较胍乙啶为优。电刺激猫迷走神经外周端引起的降压和心率变慢,给BD-38后稍有阻断,1/2小时内恢复。对乙酰胆硷的作用无明显改变。BD-38也能抑制因阻断颈总动脉引起的加压反射。离体豚鼠心肺标本,血中BD-38浓度为0.25mg/ml,对心率、心输出量无改变,浓度增至2mg/ml,也不抑制心脏。BD-38不影响洋地黄毒甙的毒性。狗亚急性毒性试验,未发现对生长和肝功能的影响。BD-38具有持久的降压效果、胃肠道吸收良好、静注无急性拟交感反应、对心脏无直接抑制作用,值得临床试用。Abstract: β-N-(cis-2, 6-dimethylpiperino)-ethyl-guanidine sulphate (BD-38) was synthesized in our Institute. Some pharmacological, mainly cardiovascular, actions were investigated.Blood pressure was markedly lowered by intravenous injection (iv) of 1~5 mg/kg or intraduodenal administration of 10 mg/kg in anaesthetized cats or iv 5 mg/kg in anaesthetized dogs. There was no significant alteration in the electrocardiogram.The guinea pig ileum was set up for periarterial nerve as well as for coaxial stimulation. When the periarterial nerves were stimulated the twitch induced by coaxial stimulation was diminished. BD-38 inhibited partly the twitch in response to coaxial stimulation, and the effects of periarterial nerve stimulation were then blocked remarkably. BD-38 inhibited significantly the hypertension caused by electrical stimulation of the distal end of splanchnic nerves in anaesthetized cats. In conscious cats, iv guanethidine sulphate or BD-38 (5 or 10 mg/kg) brought about relaxations of nictitating membranes of similar intensity. In conscious cats, intragastric garage of BD-38 (10 mg/kg) produced a relaxation of nictitating membrane to an extent of about twice that by guanethidine sulphate 10 mg/kg. An increase of the dosage of guanethidine sulphate to 20 mg/kg yielded a relaxation of nictitating membrane similar to that by BD-38 (10 mg/kg). This demonstrated that BD-38 was better absorbed in the gastrointestinal tract than guanethidine sulphate.The hypotension and bradycardia caused by electrical stimulation of peripheral end of cat vagus nerve was slightly blocked by BD-38, and restored in 1/2 hour. There was no much change toward AcCh actions. BD-38 also inhibited the pressor response from occlusion of common carotid artery.In the isolated heart-lung preparations of guinea pigs, the heart rate and cardiac output showed no change at a concentration of 0.25 mg/ml blood. At 2 mg/ml, the work of the heart was not inhibited. BD-38 did not influence the toxicities of digitoxin.Subacute toxicity experiments in dogs revealed no effect on the growths and liver functions.In conclusion, BD-38 manifested a prolonged hypotensive action, displayed good absorption from the alimentary tract, lacked acute sympathomimetic reaction after ivinjecton and disclosed no direct cardiao-inhibition. Hence it is worth while to put BD-38 into clinical trial.
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