Ranirestat as a therapeutic aldose reductase inhibitor for diabetic complications.
BACKGROUND
There are currently very few drugs available to directly treat diabetic complications. Those that are indicated clinically provide symptomatic relief and do not address the underlying biochemical problems. The involvement of the sorbitol pathway in complications has provided mechanistic insights into the biochemistry of complications and the key enzyme, aldose reductase, has become an attractive pharmacologic target.


OBJECTIVE
Among the aldose reductase inhibitors, the most promising is ranirestat. This review outlines the studies with ranirestat and compares its efficacy with other similar inhibitors.


METHODS
A survey of in vitro and in vivo studies was conducted, and with publicly available data from clinical trials, ranirestat efficacy was compared with other similar agents.


CONCLUSIONS
Ranirestat is safe, exhibits some efficacy and is perhaps the only agent advanced enough in clinical trials to warrant further consideration for diabetic complications.
Giannoukakis
Nick
N
University of Pittsburgh School of Medicine, Department of Pathology and Immunology, Diabetes Institute, Rangos Research Center, 3460 Fifth Avenue, Pittsburgh, PA 15213, USA. ngiann1@pitt.edu
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002986:Clinical Trials as Topic; D048909:Diabetes Complications / Q000188:drug therapy* / Q000201:enzymology / Q000517:prevention & control; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D013012:Sorbitol / Q000378:metabolism; D013141:Spiro Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D011719:Pyrazines; D013141:Spiro Compounds; D013012:Sorbitol; D000449:Aldehyde Reductase; C115070:ranirestat