Benzamil is an epithelial sodium channel (ENaC) blocker that inhibits sodium transport from (IC50 = 4 nM) and binds to (Kd = 5 nM) bovine kidney cortex membrane vesicles.

本研究探讨了ASICs在调节神经痛中的作用。在100-120克的雄性Sprague-Dawley大鼠上通过L4-5脊神经缚扎引起神经痛，并进行了脊髓内导管插入以便化合物给药。通过上下法评估爪撤回阈值对机械刺激的反应，测量了amiloride和benzamil的效果。同时，通过RT-PCR分析了脊髓背角ASICs的表达。脊髓内给予amiloride和benzamil显著增加了脊神经缚扎大鼠的爪撤回阈值（分别为87%±12% 和76%±14%，P=0.007和0.012 vs对照组）。脊神经缚扎增加了脊髓背角ASIC3的表达（P=0.01），而amiloride和benzamil均能抑制这一增加（P<0.001）。因此，脊髓内给药的amiloride和benzamil在大鼠脊神经缚扎模型中显示出抗痛觉影响[1]。

On the day of the experiment, rats were allocated into experimental and control groups for the tested drugs.?Control groups were performed using intrathecal DMSO (n=5) or methanol (n=5) according to the solvent used for the tested drugs.?All experiments were performed by investigators blinded to the treatment.?To assess the effects of both drugs, increasing doses of amiloride (1, 3, 10 μg in 10 μL, n=5-7) or benzamil (3, 10, 30 μg in 10 μL, n=5-7) were investigated.?The withdrawal threshold was measured prior to spinal nerve ligation and was regarded as pre-ligated threshold.?The withdrawal threshold was measured immediately prior to intrathecal drug delivery and was regarded as a post-ligated baseline threshold.?The withdrawal threshold was determined at 15, 30, 60, 90, 120, 150, and 180 min following intrathecal administration of the experimental drugs.For the purpose of examining the behavioral changes by amiloride and benzamil, the highest dose of each drug was administered intrathecally to 10 additional rats.?Motor function was assessed by the righting reflex and placing-stepping reflex[1].