Clinical experience with sorbinil—An aldose reductase inhibitor

Pitts, Norman E.; Vreeland, Franzanne; Shaw, Gerald L.; Peterson, Michael J.; Mehta, Dilip; Collier, John M.; Gundersen, Kare

doi:10.1016/0026-0495(86)90195-2

Cited by 37 publications

(5 citation statements)

References 4 publications

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“…However, it is known that most of the compounds have unacceptable side effects. Hydantoin-type inhibitors have a risk of Steven−Johnson syndrome and hypersensitivity reaction ( , ). On the other hand, many carboxylic acid derivatives have also been withdrawn from clinical trials due to lack of efficacy or toxicity ( , ).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Effects ofZingiber officinaleRoscoe Derived Components on Aldose Reductase Activity in Vitro and in Vivo

Kato

Higuchi

Goto

et al. 2006

J. Agric. Food Chem.

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Ginger (Zingiber officinale Roscoe) continues to be used as an important cooking spice and herbal medicine around the world. Scientific research has gradually verified the antidiabetic effects of ginger. Especially gingerols, which are the major components of ginger, are known to improve diabetes including the effect of enhancement against insulin-sensitivity. Aldose reductase inhibitors have considerable potential for the treatment of diabetes, without increased risk of hypoglycemia. The assay for aldose reductase inhibitors in ginger led to the isolation of five active compounds including 2-(4-hydroxy-3-methoxyphenyl)ethanol (2) and 2-(4-hydroxy-3-methoxyphenyl)ethanoic acid (3). Compounds 2 and 3 were good inhibitors of recombinant human aldose reductase, with IC50 values of 19.2 +/- 1.9 and 18.5 +/- 1.1 microM, respectively. Furthermore, these compounds significantly suppressed not only sorbitol accumulation in human erythrocytes but also lens galactitol accumulation in 30% of galactose-fed cataract rat model. A structure-activity relationship study revealed that the applicable side alkyl chain length and the presence of a C3 OCH3 group in the aromatic ring are essential features for enzyme recognition and binding. These results suggested that it would contribute to the protection against or improvement of diabetic complications for a dietary supplement of ginger or its extract containing aldose reductase inhibitors.

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Section: Introductionmentioning

confidence: 99%

Inhibitory Effects ofZingiber officinaleRoscoe Derived Components on Aldose Reductase Activity in Vitro and in Vivo

Kato

Higuchi

Goto

et al. 2006

J. Agric. Food Chem.

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“…For example, the ARIs sorbinil, tolrestat and alrestatin were efficacious but caused severe side effects in a small patient population. Sorbinil caused hypersensitivity reactions similar to diphenylhydantoin (Pitts et al 1986;Sarges et al 1988) and it was speculated that the hydantoin moiety common to sorbinil and diphenylhydantoin was the cause for this hypersensitivity (Jaspan et al 1985). With tolrestat, the major side effect was hepatic damage with concomitant elevation of liver enzymes in 2% of the patients (Macleod et al 1992).…”

Section: Introductionmentioning

confidence: 99%

Systemic and ocular pharmacokinetics of N-4-benzoylaminophenylsulfonylglycine (BAPSG), a novel aldose reductase inhibitor

Sunkara

Ayalasomayajula

Rao

et al. 2004

Journal of Pharmacy and Pharmacology

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To better develop N- [4-(benzoylamino)phenylsulfonyl]glycine (BAPSG), a potent and selective aldose reductase inhibitor capable of delaying the progression of ocular diabetic complications, the objective of this study was to assess its pharmacokinetics. The plasma pharmacokinetics of BASPG was assessed in male Sprague-Dawley rats following intravenous, intraperitoneal and oral routes of administration and its distribution to various tissues including those of the eye was studied following intraperitoneal administration. In addition, rat plasma protein binding of BAPSG was studied using ultracentrifugation method and its ocular tissue disposition was assessed following topical administration in rabbits. Plasma and tissue levels of BAPSG were analysed using an HPLC assay. BAPSG exhibited dose-proportionate AUC 0→∞ (area under the plasma HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript concentration-time curve) following both intravenous and intraperitoneal administration over the dose range (5-50 mg kg −1 ) studied and an erratic oral absorption profile with low oral bioavailability. The fraction bioavailability following oral and intraperitoneal administration was 0.06 and 0.7-1, respectively. BAPSG exhibited short plasma elimination half-lives in the range 0.5-1.5 h. BAPSG was bound to rat plasma proteins and the percent protein binding ranged from 83 to 99.8%. BAPSG was better distributed to cornea, lens and retina than to brain, following intraperitoneal administration in rats. However, the distribution was lower compared with kidney and liver. Following topical administration in rabbits, BAPSG delivery to the surface ocular tissues, cornea and conjunctiva was higher compared with intraocular tissues, aqueous humour, iris-ciliary body and lens. Thus, BAPSG was distributed to ocular tissues following systemic and topical modes of administration.

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“…However, it is known that most of the compounds have unacceptable side effects. Hydantointype inhibitors have a risk of Steven-Johnson syndrome and hypersensitivity reaction (Pitts et al, 1986;Spielberg et al, 1991). On the other hand, many carboxylic acid derivatives have also been withdrawn from clinical trials due to lack of efficacy or toxicity (Sarges, 1989;Humber, 1987).…”

Section: Introductionmentioning

confidence: 99%

Antihyperglycaemic and aldose reductase inhibitory potential of Acacia catechu hard wood and Tectona grandis leaves

Bhatia

Srivastava

et al. 2010

Med Chem Res

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The ethanolic extract of Acacia catechu hard wood (Ac) and the ethanolic as well as aqueous extracts of Tectona grandis leaves (Tg) showed marked antihyperglycaemic activity in both normoglycaemic and streptozotocininduced diabetic rats at 250 mg/kg dose levels. The ethanolic and aqueous extracts of Ac and Tg also showed marked inhibition on AR from eye lens of normal rats with IC 50 values of 9.30 and 9.08 and 3.05, 4.51 lg/ml, respectively. The ethanolic as well as aqueous extracts of both Ac and Tg also showed marked inhibition on AR from eye lens of STZinduced diabetic rats with IC 50 values of 4.70 and 4.91 and 4.71 and 4.83 lg/ml. These results suggest that Acacia catechu hard wood and Tectona grandis leaves could be a new approach in the development of therapeutic or preventive agents for diabetic late-stage complications.

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Clinical experience with sorbinil—An aldose reductase inhibitor

Cited by 37 publications

References 4 publications

Inhibitory Effects ofZingiber officinaleRoscoe Derived Components on Aldose Reductase Activity in Vitro and in Vivo

Inhibitory Effects ofZingiber officinaleRoscoe Derived Components on Aldose Reductase Activity in Vitro and in Vivo

Systemic and ocular pharmacokinetics of N-4-benzoylaminophenylsulfonylglycine (BAPSG), a novel aldose reductase inhibitor

Antihyperglycaemic and aldose reductase inhibitory potential of Acacia catechu hard wood and Tectona grandis leaves

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