Alrestatin Explained

Alrestatin is an inhibitor of aldose reductase, an enzyme involved in the pathogenesis of complications of diabetes mellitus, including diabetic neuropathy.^{[1] [2]}

Alrestat was first synthesized in 1969 and was the first aldose reductase inhibitor (ARI) with oral bioavailability to undergo clinical trials, in the late 1970s and early 1980s. Low-quality trials and a high incidence of adverse effects (particularly hepatotoxicity) led to termination of its development, and it was never in clinical use.^{[3] [4]} It is structurally related to tolrestat, another ARI that was briefly marketed before being withdrawn in 1997.

Synthesis

Alrestatin can be synthesized by the reaction of naphthalic anhydride with glycine.^[5]

See also

• Amonafide
• Scriptaid

Notes and References

1. Gabbay KH, Spack N, Loo S, Hirsch HJ, Ackil AA . Aldose reductase inhibition: studies with alrestatin . Metab Clin Exp . 28 . 4 Suppl 1 . 471–6 . April 1979 . 122298 . 10.1016/0026-0495(79)90059-3.
2. Ehrig T, Bohren KM, Prendergast FG, Gabbay KH . Mechanism of aldose reductase inhibition: binding of NADP+/NADPH and alrestatin-like inhibitors . Biochemistry . 33 . 23 . 7157–65 . June 1994 . 8003482 . 10.1021/bi00189a019.
3. Book: Striker, Gary E. . Gueriguian, John L. . Diabetic complications: epidemiology and pathogenetic mechanisms . Raven Press . New York . 1991 . 293–4 . 0-88167-648-9.
4. Book: Veves, Aristidis . Rayaz A., Malik . Veves, Aristidis . Diabetic Neuropathy: Clinical Management . Aldose reductase inhibitors for the treatment of diabetic neuropathy . Humana Press . Totowa, NJ . 2007 . 309–11 . 978-1-59745-311-0 . https://books.google.com/books?id=dMKoFySox7kC&pg=PA310 . 2013-02-13.
5. Ayerst Mckenna & Harrison,