Epalrestat

Source: Wikipedia, the free encyclopedia.
Epalrestat
Names
Preferred IUPAC name
{(5Z)-5-[(2E)-2-Methyl-3-phenylprop-2-en-1-ylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl}acetic acid
Identifiers
3D model (
JSmol
)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard
 100.200.343 Edit this at Wikidata
KEGG
UNII
  • InChI=1S/C15H13NO3S2/c1-10(7-11-5-3-2-4-6-11)8-12-14(19)16(9-13(17)18)15(20)21-12/h2-8H,9H2,1H3,(H,17,18)/b10-7+,12-8- ☒N
    Key: CHNUOJQWGUIOLD-NFZZJPOKSA-N ☒N
  • InChI=1/C15H13NO3S2/c1-10(7-11-5-3-2-4-6-11)8-12-14(19)16(9-13(17)18)15(20)21-12/h2-8H,9H2,1H3,(H,17,18)/b10-7+,12-8-
    Key: CHNUOJQWGUIOLD-NFZZJPOKBR
  • O=C(O)CN1C(=O)C(\SC1=S)=C/C(=C/c2ccccc2)C
Properties
C15H13NO3S2
Molar mass 319.401 g/mol
Density 1.43 g/cm3
Melting point 210 °C (410 °F; 483 K)
Boiling point 516.8 °C (962.2 °F; 789.9 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Epalrestat is a carboxylic acid derivative

diabetes mellitus. It reduces the accumulation of intracellular sorbitol which is believed to be the cause of diabetic neuropathy, retinopathy and nephropathy [2][3] It is well tolerated, with the most commonly reported adverse effects being gastrointestinal issues such as nausea and vomiting, as well as increases in certain liver enzymes.[4]
Chemically, epalrestat is unusual in that it is a drug that contains a rhodanine group. Aldose reductase is the key enzyme in the polyol pathway whose enhanced activity is the basis of diabetic neuropathy. Aldose reductase inhibitors (ARI) target this enzyme. Out of the many ARIs developed, ranirestat and fidarestat are in the trial stage. Others have been discarded due to unacceptable adverse effects or weak efficacy. Epalrestat is the only ARI commercially available.[5] It is easily absorbed into the neural tissue[6] and inhibits the enzyme with minimum side effects.[7]

Evidence

It has been demonstrated in animal experiments that there is an improvement in sorbitol levels and Na+/K+ ATPase activity leading to improved nerve conduction velocity. Diabetic rats treated with epalrestat showed improvement in morphological abnormalities of nerves.[8] In a placebo controlled double blind trial of 196 patients, it was shown that Epalrestat in a dose of 150 mg/day improved the effects of diabetic neuropathy like upper limb spontaneous pain, motor nerve conduction velocity, thresholds of vibratory sensation and autonomic nerve function as compared to a placebo. These effects were significantly better in those with poorer control of diabetes.[9] A systematic review and metaanalysis showed that based on the results of 10 articles, it can be concluded that Epalrestat has some benefit in the control of diabetic cardiovascular autonomic neuropathy but only in the early or mild cases. It also doesn't influence glycaemic control.[10]

Brand names

  • Aldonil (Zydus Medica), India
  • Aldorin, Bangladesh
  • Alrista (marketed and not manufactured by Macleods), India
  • Epalrica-M (Ordain Global), India
  • Eparel 50 (Microlabs Ltd), India
  • Epimeth (Zaiva Lifesciences), India
  • Eplistat 150 SR (Schem), India
  • Letostat-SR (Amor Pharmaceuticals), India
  • Listap-50 (Vivid Biotek), India
  • Tanglin (Yangtze River Pharmaceutical Group), China

References

  1. PMID 6423811
    .
  2. S2CID 207233270
    .
  3. PMID 8312678
    .
  4. S2CID 207233270
    .
  5. PMID 16801576
    . Retrieved 16 July 2016.
  6. PMID 6423811
    .
  7. PMID 8807467
    .
  8. ^ Hotta, N; Sugimura, K; Kakuta, H; Fukasawa, H; Kimura, M; Koh, N (1988). Effects of a fructose rich diet and an aldose reductase inhibitor on the development of diabetic neuropathy in streptozotocin-treated rats. Amsterdam: Elsevier Science Publishers BV. p. 511.
  9. PMID 7579007
    .
  10. PMID 24533052
    .

External links


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