Cuthbert A W, Fanelli G M
Br J Pharmacol. 1978 May;63(1):139-49. doi: 10.1111/j.1476-5381.1978.tb07783.x.
1 The inhibitory effect of amiloride (N-amidino-3,5-diamino-6-chloropyrazinecarboxamide) on sodium transport in isolated skin of frog has been compared with 17 of its analogues. The dissociation constant of amiloride for passive sodium channels was 181.9 +/- 8.9 nM, and the maximal percentage inhibition of sodium transport was 101.3 +/- 0.4% (means of 123 measurements) when measured at a sodium concentration of 111 mM. 2 The N-benzylamidino and N-o-chlorobenzylamidino compounds had affinities approximately 20 times larger than those for amiloride, and produced maximal inhibition of transport. 3 Substitution of chlorine in the 6-position by other halogens showed that the bromo-compound was equally active to amiloride, whereas the iodo derivative had an affinity equal to 15% of that for amiloride. 4 Substitution in the 5-amino group in 10 compounds reduced the affinities to less than 1% of that of amiloride, without affecting their ability to produce complete inhibition of transport. 5 N-Amidino-3,5-diaminopyrazinecarboxamide was unique in that it produced an unusual concentration-response relationship.
1 已将氨氯地平（N-脒基-3,5-二氨基-6-氯吡嗪甲酰胺）与其17种类似物对蛙离体皮肤钠转运的抑制作用进行了比较。氨氯地平对被动钠通道的解离常数为181.9±8.9 nM，在钠浓度为111 mM时测量，钠转运的最大抑制百分比为101.3±0.4%（123次测量的平均值）。2 N-苄基脒基和N-邻氯苄基脒基化合物的亲和力比氨氯地平的亲和力大约大20倍，并产生最大转运抑制作用。3 在6位用其他卤素取代氯表明，溴代化合物与氨氯地平活性相当，而碘代衍生物的亲和力等于氨氯地平的15%。4 10种化合物中5-氨基的取代使亲和力降低至氨氯地平的1%以下，而不影响它们产生完全转运抑制的能力。5 N-脒基-3,5-二氨基吡嗪甲酰胺的独特之处在于它产生了一种不寻常的浓度-反应关系。
