Sugino H, Shimada H
Department of Clinical Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Jpn J Pharmacol. 1995 Jul;68(3):297-303. doi: 10.1254/jjp.68.297.
N-[3-[4'-(2",6"-Dimethylheptyl)phenyl]butanoyl]ethanolamine (E5050), a newly synthesized compound, was shown recently to induce uricosuria in humans via inhibition of the postsecretory reabsorption of urate. We examined the effects of this compound on urate excretion in rats loaded with oxonate and compared these effects with those of the uricosuric drugs trichlormethiazide and probenecid. When administered i.p., E5050 (0.3-15 mg/kg) increased the urinary excretion rate of urate and the ratio of urate clearance to inulin clearance in a dose-dependent manner, while the urine volume increased only slightly, and the glomerular filtration rate and plasma urate level were not changed. No paradoxical effect on urate excretion was observed. In contrast, trichlormethiazide and probenecid had a biphasic effect on urate excretion. In a pyrazinoic acid suppression test, the uricosuric effect of E5050 was completely inhibited by pretreatment with pyrazinoic acid. In a phenolsulfonphthalein (PSP) test, E5050 did not affect urinary PSP excretion, while probenecid strongly decreased such excretion. Thus, E5050 also appears to be uricosuric in rats.
N-[3-[4'-(2",6"-二甲基庚基)苯基]丁酰基]乙醇胺（E5050）是一种新合成的化合物，最近研究表明它可通过抑制尿酸分泌后的重吸收来诱导人体尿酸尿。我们研究了该化合物对氧嗪酸钾负荷大鼠尿酸排泄的影响，并将这些影响与促尿酸尿药物三氯噻嗪和丙磺舒的影响进行比较。腹腔注射E5050（0.3 - 15毫克/千克）时，尿酸排泄率及尿酸清除率与菊粉清除率的比值呈剂量依赖性增加，而尿量仅略有增加，肾小球滤过率和血浆尿酸水平未发生变化。未观察到对尿酸排泄的矛盾效应。相比之下，三氯噻嗪和丙磺舒对尿酸排泄有双相效应。在吡嗪酸抑制试验中，用吡嗪酸预处理可完全抑制E5050的促尿酸尿作用。在酚红（PSP）试验中，E5050不影响尿PSP排泄，而丙磺舒则显著降低其排泄。因此，E5050在大鼠中似乎也具有促尿酸尿作用。
