title: Fidarestat (SNK-860), a potent aldose reductase inhibitor, normalizes the elevated sorbitol accumulation in erythrocytes of diabetic patients.
abstract: Sorbitol accumulation in nerves has been regarded as one of the major causes of diabetic neuropathy. In this study, fidarestat (SNK-860; 1 mg daily), a potent new aldose reductase inhibitor (ARI), or the commercially available ARI epalrestat (150 mg daily), was administered for 4 weeks to 58 Type 2 diabetic patients. Treatment with these drugs had no effect on glycemic control, judging from plasma glucose and HbA(1c) levels. However, fidarestat treatment normalized the elevated sorbitol content of erythrocytes under fasting as well as postprandial conditions. In contrast, the effect of epalrestat was minimal. There were no major side effects with fidarestat. Thus, fidarestat is considered to be a potent and promising ARI, possibly useful for both preventing and treating diabetic neuropathy. Further studies are needed to clarify how much the occurrence and progression of diabetic neuropathy are inhibited by normalizing sorbitol elevation with fidarestat treatment.
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113, Tokyo, Japan. asano-tky@umin.ac.jp
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Asano
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kawakami
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yamada
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000097:blood / Q000494:pharmacology*; D048289:Imidazolidines; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012236:Rhodanine / Q000031:analogs & derivatives / Q000494:pharmacology*; D013012:Sorbitol / Q000097:blood*; D053778:Thiazolidines
chemical_list: D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D053778:Thiazolidines; C038131:epalrestat; D013012:Sorbitol; D012236:Rhodanine; C077139:fidarestat; D000449:Aldehyde Reductase