Cohn R C, Rudzienski L, Putnam R W
Department of Pediatrics, Wright State University, Dayton, Ohio.
Chemotherapy. 1992;38(4):232-7. doi: 10.1159/000239006.
The effects of specific amiloride analogs on Na+ channel and Na+/H+ antiport function in eukaryotic cells have been well studied, but the effect of these agents on Pseudomonas is unknown. The antimicrobial activity of benzamil HCl, 5-(N-N-dimethyl)amiloride HCl (DMA), 5-(N,N-hexamethylene)amiloride HCl (HMA), and 5-(N-methyl-N-isobutyl)amiloride HCl (MIA) on 30 Pseudomonas strains (20 P. aeruginosa and 10 P. cepacia) were compared to amiloride HCl after a 24-hour incubation in Mueller-Hinton broth at 35 degrees C. At pH 7.3 the MIC range and MIC50 (in mg/l; MIC50 in parentheses) for amiloride HCl, benzamil HCl, DMA, HMA and MIA were 400 to > 800 (> 800), 200 to 800 (400), 200 to > 800 (400), 100 to 400 (200), and 100 to 400 (200), respectively, for P. aeruginosa and > 800 (> 800), 400 to > 800 (800), 400 to > 800 (800), 200 to 800 (200), and 200 to 800 (200), respectively, for P. cepacia. Alteration of pH from 5.5 to 8.5 had a slight effect on potency. We conclude that all the analogs studied were more potent antipseudomonal agents in vitro than amiloride, with the more lipophilic compounds HMA and MIA, having the most profound activity.
特定氨氯吡咪类似物对真核细胞中钠通道和钠/氢逆向转运蛋白功能的影响已得到充分研究，但这些药物对铜绿假单胞菌的影响尚不清楚。将盐酸苯甲米、5-（N-N-二甲基）氨氯吡咪盐酸盐（DMA）、5-（N，N-六亚甲基）氨氯吡咪盐酸盐（HMA）和5-（N-甲基-N-异丁基）氨氯吡咪盐酸盐（MIA）对30株铜绿假单胞菌（20株铜绿假单胞菌和10株洋葱伯克霍尔德菌）的抗菌活性与盐酸氨氯吡咪在35℃的穆勒-欣顿肉汤中孵育24小时后进行比较。在pH 7.3时，盐酸氨氯吡咪、盐酸苯甲米、DMA、HMA和MIA对铜绿假单胞菌的MIC范围和MIC50（以mg/l为单位；括号内为MIC50）分别为400至>800（>800）、200至800（400）、200至>800（400）、100至400（200）和100至400（200），对洋葱伯克霍尔德菌分别为>800（>800）、400至>800（800）、400至>800（800）、200至800（200）和200至800（200）。将pH从5.5改变至8.5对效力有轻微影响。我们得出结论，所有研究的类似物在体外都是比氨氯吡咪更有效的抗铜绿假单胞菌药物，亲脂性更强的化合物HMA和MIA具有最显著的活性。
