Epalrestat-d5

Epalrestat-d₅ is intended for use as an internal standard for the quantification of epalrestat by GC- or LC-MS. Epalrestat is an inhibitor of aldose reductase (IC₅₀s = 0.01 and 0.26 µM for rat lens and human placenta aldose reductase, respectively).¹ It inhibits glucose-induced sorbitol accumulation in isolated rat lens, rat sciatic nerve, and human erythrocytes (IC₅₀s = 1.5, 5, and 1.5 µM, respectively). It decreases high glucose-induced proliferation of vascular smooth muscle cells when used at a concentration of 10 nM and prevents high glucose-induced intracellular NADH/NAD⁺ increases and membrane-bound PKC activation at 100 nM.^2,3 Epalrestat (20 and 40 mg/kg) improves motor nerve conduction velocity and decreases sorbitol content in the sciatic nerve and erythrocytes in a rat model of streptozotocin-induced diabetic neuropathy.⁴ It also prevents capillary strand formation in a rat model of diabetes-induced retinal microangiopathy when administered at a dose of 50 mg/kg.⁵

1.Terashima, H., Hama, K., Yamamoto, R., et al.Effects of a new aldose reductase inhibitor on various tissues in vitroJ. Pharmacol. Exp. Ther.229(1)226-230(1984) 2.Yasunari, K., Kohno, M., Kano, H., et al.Aldose reductase inhibitor improves insulin-mediated glucose uptake and prevents migration of human coronary artery smooth muscle cells induced by high glucoseHypertension35(5)1092-1098(2000) 3.Yasunari, K., Kohno, M., Kano, H., et al.Aldose reductase inhibitor prevents hyperproliferation and hypertrophy of cultured rat vascular smooth muscle cells induced by high glucoseArterioscler. Thromb. Vasc. Biol.15(12)2207-2212(1995) 4.Kikkawa, R., Hatanaka, I., Yasuda, H., et al.Effect of a new aldose reductase inhibitor, (E)-3-carboxymethyl-5-[(2E)-methyl-3-phenylpropenylidene]rhodanine (ONO-2235) on peripheral nerve disorders in streptozotocin-diabetic ratsDiabetologia24(4)290-292(1983) 5.Kojima, K., Matsubara, H., Mizuno, K., et al.Experimentally induced diabetic retinal microangiopathy and polyol pathway. II. Effect of aldose reductase inhibitors on microangiopathyNippon Ganka Gakkai Zasshi89(2)247-256(1985)