We investigated the effects of three aldose reductase (AR) inhibitors, fidarestat, epalrestat and zenarestat, on the slowing of sensory nerve conduction velocity (SNCV), motor nerve conduction velocity (MNCV), and min...
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We investigated the effects of three aldose reductase (AR) inhibitors, fidarestat, epalrestat and zenarestat, on the slowing of sensory nerve conduction velocity (SNCV), motor nerve conduction velocity (MNCV), and minimal F-wave latency prolongation in streptozotocin (STZ)-induced diabetic rats. Two weeks after STZ injection, SNCV and MNCV in the diabetic rats were significantly slower than in normal rats. Fidarestat (0.25-2 mg/kg/day), epalrestat (48 to 96 mg/kg/day) or zenarestat (10-40 mg/kg/day) was administered orally for the following 2 weeks, and SNCV, MNCV and F-wave latency were measured 3 h after final administration. Significant prolongation of minimal F-wave latency, as well as slowing of SNCV and MNCV, was found in the untreated diabetic rats 4 weeks after STZ injection. At a dose of 0.5 mg/kg/day or more fidarestat showed significant effects on these nervous dysfunctions, effects that were more potent than those shown by the other inhibitors. Furthermore, following the 2-week administration of fidarestat (1 mg/kg/day), epalrestat (48 mg/kg/day) or zenarestat (20 mg/kg/day), which began 2 weeks after STZ injection, sorbitol content in the sciatic nerve, produced by AR, a rate-limiting enzyme in the polyol pathway, was determined at 3, 8, 12, and 24 h after final administration. At each point in time, sorbitol content in the untreated diabetic rats was much higher than that in the normal control rats. Fidarestat suppressed sorbitol accumulation remarkably and continuously until 24 h after administration. On the other hand, the inhibitory effect by zenarestat declined in a time-dependent manner, and epalrestat did not decrease sorbitol content. Therefore, these results suggest that continuous inhibition of increased polyol pathway flux can improve diabetic neuropathy more potently. (C) 1999 Elsevier Science Inc.
【目的】观察依帕司他联合前列地尔治疗糖尿病周围神经病变（DPN）的临床疗效。【方法】将88例2型糖尿病（T2DM）DPN的患者随机分为对照组与观察组，各44例，两组患者均严格控制饮食、适量运动、口服降糖药或注射胰岛素控制血糖，甲钴胺注射液0．5 mg肌注，每日1次。在此基础上，观察组加用依帕司他50 mg口服，每日3次；前列地尔20μg＋0．9％氯化钠注射液100 m L静脉滴注，每日1次。疗程均为2周。【结果】观察组患者自觉症状改善总有效率（97．7％）显著高于对照组（72．7％）（P＜0．05）；两组神经传导速度（NCV）均明显改善，观察组优于对照组，差异具有统计学意义（P＜0．01）。【结论】依帕司他、前列地尔及甲钴胺注射液联合治疗DPN效果显著。
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