Misu Y, Nishio H, Hosotani T, Hamano S
Jpn J Pharmacol. 1976 Jun;26(3):367-75. doi: 10.1254/jjp.26.367.
Effects of 4-7-exo-methylene-hexahydroisoindoline-ethyl-guanidine hemisulfate (No. 865-123), a new guanidine derivative, on adrenergic neurons and its local anesthetic activity were investigated in comparison with guanethidine. Both derivatives produced in a dose-dependent manner a progressive irreversible reduction of positive chronotropic and contractile responses to postganglionic sympathetic nerve stimulation in isolated rabbit atria. The time course of the reduction by No. 865-123 was somewhat slower. In dogs administered both agents, the pressor response to carotid occlusion was reduced and that to exogenous noradrenaline was potentiated with a slight decrease in blood pressure. Noradrenaline stores in the heart and spleen of rats were also depleted to a similar extent. In the guinea pig weal method, guanethidine acted as a potent local anesthetic with a slow onset and a prolonged action as compared to procaine. No. 865-123 revealed no more anesthetic activity than did saline. It is unlikely that the local anesthetic activity of the guanidine derivatives contributes to the adrenergic neuron blocking activity.
研究了新型胍衍生物4-7-外向亚甲基-六氢异吲哚啉-乙基-胍半硫酸盐（编号865-123）对肾上腺素能神经元的作用及其局部麻醉活性，并与胍乙啶进行了比较。两种衍生物均以剂量依赖性方式，使离体兔心房对节后交感神经刺激的正性变时和收缩反应逐渐出现不可逆降低。865-123引起降低的时间进程稍慢一些。给犬施用这两种药物后，对颈动脉闭塞的升压反应降低，对外源性去甲肾上腺素的反应增强，同时血压略有下降。大鼠心脏和脾脏中的去甲肾上腺素储备也被消耗至相似程度。在豚鼠风团法中，与普鲁卡因相比，胍乙啶是一种起效缓慢、作用持久的强效局部麻醉剂。865-123的麻醉活性并不比生理盐水更强。胍衍生物的局部麻醉活性不太可能导致其肾上腺素能神经元阻断活性。
