Aldose reductase inhibitors

General information

Aldose reductase inhibitors [ ] have been developed for the treatment of secondary complications in diabetes [ , ]. They include alrestatin, benurestat, epalrestat, fidarestat, imirestat, lidorestat, minalrestat, ponalrestat, ranirestat, risarestat, sorbinil, tolrestat, zenarestat, and zopolrestat.

The aldose reductase inhibitors inhibit or reduce secondary complications induced by diabetes, specifically in tissues in which glucose uptake is not insulin-dependent (probably neural tissue, the lens, and glomeruli). Many of them (including alrestatin, imirestat, ponalrestat, and sorbinil) have been used in clinical trials, but have been withdrawn because of adverse effects or lack of effect [ ]. Their main adverse effects include fever, nausea, diarrhea, increases in liver enzymes, skin rashes, including toxic epidermal necrolysis and Stevens–Johnson syndrome, marked thrombocytopenia, lymphadenopathy, splenomegaly, and adult respiratory distress syndrome.

Tolrestat was withdrawn because of deaths from fatal hepatic necrosis [ ] and poor efficacy in clinical trials. Sorbinil was withdrawn because of hypersensitivity reactions in more than 10% of patients.

Organs and systems