Amaki Y, Koyama T, Wada T, Kobayashi K, Futaki R
Masui. 1989 May;38(5):661-5.
A new muscle relaxant antagonist, 4-aminopyridine (4-AMP), has various problems related to its side effects. In order to obtain 4-AMP derivatives with less side effect and the same antagonizing effect on dTc block as that of 4-AMP, three types of derivatives were synthesized. They were 4-methylaminopyridine (4-MAMP), 4-dimethylaminopyridine (4-DAMP), and 4-trimethylaminopyridine (4-TAMP). For the purpose of studying their effects on neuromuscular junction, the antagonistic effects of the three derivatives on the dTc block were compared with those of 4-AMP, by using rat diaphragm preparation in vitro, and rat sciatic nerve tibialis anterior muscle preparation in vivo. These three derivatives exhibited earlier onset time compared with 4-AMP, but their efficacy was lower in terms of ED50 in vivo and in vitro. Also their duration of effect was shorter than 4-AMP. In particular, the ED50 of 4-DAMP was much larger (9 times that of 4-AMP), and its duration of effect was shorter (11 minutes), indicating that it is unsuitable as a practical antagonistic agent. ED50 of 4-TAMP was the closest to that of 4-AMP (three times that of 4-AMP), and it exhibited effects earlier than 4-AMP (one fourth that of 4-AMP), but was inferior in duration of effect (13 minutes). With respect to antagonistic effects, these three agents cannot be described as perfect, and development of new derivatives will be required.
一种新型肌肉松弛拮抗剂4-氨基吡啶（4-AMP）存在各种与其副作用相关的问题。为了获得副作用较小且对筒箭毒碱（dTc）阻滞具有与4-AMP相同拮抗作用的4-AMP衍生物，合成了三种类型的衍生物。它们分别是4-甲基氨基吡啶（4-MAMP）、4-二甲基氨基吡啶（4-DAMP）和4-三甲基氨基吡啶（4-TAMP）。为了研究它们对神经肌肉接头的影响，通过体外大鼠膈肌制备以及体内大鼠坐骨神经胫前肌制备，将这三种衍生物对dTc阻滞的拮抗作用与4-AMP的进行了比较。与4-AMP相比，这三种衍生物起效时间更早，但在体内和体外的半数有效量（ED50）方面其效力较低。而且它们的作用持续时间比4-AMP短。特别是，4-DAMP的ED50大得多（是4-AMP的9倍），其作用持续时间短（11分钟），表明它不适合作为实际的拮抗药。4-TAMP的ED50最接近4-AMP的（是4-AMP的3倍），并且其起效比4-AMP早（是4-AMP的四分之一），但其作用持续时间较差（13分钟）。就拮抗作用而言，这三种药物都不能说是完美的，因此需要开发新的衍生物。
