Minalrestat(ARI-509) is an orally active and potent aldose reductase inhibitor for the study of impaired microvascular reactivity in diabetic patients.

Minalrestat (100 μM) reduces intracellular sorbitol content in primary cultured rat cells without affecting intracellular glucose levels.[3]
Minalrestat (100 μM, 48 h) causes the accumulation of PKC-α and -β2 in primary cultured rat mesangial cells.[3]

The diabetic group was treated from 3 days after the alloxan injection with Minalrestat (10 mg/kg/day) for 30 days and the Minalrestat treatment (10 mg/kg/day/7 days) of galactosemic rats started concomitantly with the induction of galactosemia. The impaired responses to bradykinin, histamine, and platelet-activating factors of arterioles and venules observed in diabetic and galactosemic rats were completely prevented by Minalrestat. Neither diabetes nor galactosemia affected responses to acetylcholine and sodium nitroprusside. Responses to these agents were not modified by aldose reductase inhibition. The restoring effect of Minalrestat was reversed by inhibition of nitric oxide (NO) synthesis with N(omega)-nitro-L-arginine methyl ester, by blocking K(+) channel with tetraethylammonium but not by cyclooxygenase inhibition with diclofenac.[1]