エパルレスタット
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出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2016/07/17 23:01:15」(JST)
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Epalrestat
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Names |
IUPAC name
2-[(5Z)-5-[(E)-2-methyl-3-phenylprop-2-enylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid
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Identifiers |
CAS Number
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82159-09-9 Y |
ChEBI |
CHEBI:31539 N |
ChEMBL |
ChEMBL56337 N |
ChemSpider |
1285910 N |
Jmol 3D model |
Interactive image
Interactive image |
KEGG |
D01688 Y |
PubChem |
1584822 |
UNII |
424DV0807X N |
InChI
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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-SMTGYRLFSA-N N
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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-SMTGYRLFBD
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SMILES
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CC(=CC1=CC=CC=C1)C=C2C(=O)N(C(=S)S2)CC(=O)O
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O=C(O)CN1C(=O)C(\SC1=S)=C/C(=C/c2ccccc2)C
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Properties |
Chemical formula
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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).
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N verify (what is YN ?) |
Infobox references |
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Epalrestat is a carboxylic acid derivative[1] and a noncompetitive and reversible aldose reductase inhibitor used for the treatment of diabetic neuropathy, which is one of the most common long-term complications in patients with 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]
Contents
- 1 Evidence
- 2 Brand names
- 3 References
- 4 External links
Evidence
It has been proven 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 proved 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
- ^ Terashima, H; Hama, K (1984). "Effects of a new aldose reductase inhibitor on various tissue in vitro". J Pharamacol Exp Ther 229: 226–230.
- ^ Ramirez, Mary Ann; Borja, Nancy L (May 2008). "Epalrestat: An Aldose Reductase Inhibitor for the Treatment of Diabetic Neuropathy". Pharmacotherapy 28 (5): 646–655. doi:10.1592/phco.28.5.646.
- ^ Steele, John W.; Faulds, Diana; Goa, Karen L. (1993). "Epalrestat". Drugs & Aging 3 (6): 532–555. doi:10.2165/00002512-199303060-00007.
- ^ Ramirez, Mary Ann; Borja, Nancy L (May 2008). "Epalrestat: An Aldose Reductase Inhibitor for the Treatment of Diabetic Neuropathy". Pharmacotherapy 28 (5): 646–655. doi:10.1592/phco.28.5.646.
- ^ Hotta, N; Akanuma, Y; Kawamori, R; Matsuoka, K; Oka, Y; Shichiri, M (July 2006). "Long-Term Clinical Effects of Epalrestat, an". Diabetes Care 29 (7): 1538-44. doi:10.2337/dc05-2370. PMID 16801576. Retrieved 16 July 2016.
- ^ Terashima, H; Hama, K; Yamamoto, R; Tsuboshima, M; Kikkawa, R; Hatanaka, I (1984). "Effects of a new aldose reductase inhibitor on various tissues in vitro.". J Pharmacol Exp Ther 229: 226-30.
- ^ Hotta, N; Sakamoto, N; Shigeta, Y; Kikkawa, G; Goto, Y; Diabetic Neuropathy Study (1996). "Clinical investigation of epalrestat, an aldose reductase inhibitor, on diabetic neuropathy in Japan: multicenter study.". J Diabetes Complications 10: 168-72.
- ^ 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.
- ^ Goto, Y; Hotta, N; Shigeta, Y; Sakamoto, N; Kikkawa, R (1995). "Effects of an aldose reductase inhibitor, epalrestat, on diabetic neuropathy. Clinical benefit and indication for the drug assessed from the results of a placebo-controlled double-blind study.". Biomed Pharmacother 49 (6): 269-77. doi:10.1016/0753-3322(96)82642-4. PMID 7579007. Retrieved 16 July 2016.
- ^ Xin, Hu; Li, Shengbing; Yang, Gangyi; Liu, Hua; Boden, Guenther; Li, Ling (2014). "Efficacy and Safety of Aldose Reductase Inhibitor for the Treatment of Diabetic Cardiovascular Autonomic Neuropathy: Systematic Review and Meta-Analysis". PLoS One 9 (2): e87096. doi:10.1371/journal.pone.0087096. Retrieved 16 July 2016.
External links
- Epalrestat at chemblink.com
Oral anti-diabetic drugs, insulins and insulin analogs, and other drugs used in diabetes (A10)
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Insulin |
Sensitizers |
Biguanides |
- Buformin‡
- Metformin#
- Phenformin‡
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TZDs/"glitazones" (PPAR) |
- Ciglitazone§
- Darglitazone§
- Englitazone§
- Lobeglitazone
- Netoglitazone§
- Pioglitazone
- Rivoglitazone†
- Rosiglitazone
- Troglitazone‡
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Dual PPAR agonists |
- Aleglitazar†
- Muraglitazar§
- Saroglitazar
- Tesaglitazar§
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Secretagogues |
K+ATP |
Sulfonylureas |
- 1st generation: Acetohexamide
- Carbutamide
- Chlorpropamide
- Glycyclamide
- Metahexamide
- Tolazamide
- Tolbutamide
- 2nd generation: Glibenclamide (glyburide)#
- Glibornuride
- Glicaramide
- Gliclazide
- Glimepiride
- Glipizide
- Gliquidone
- Glisoxepide
- Glyclopyramide
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Meglitinides/"glinides" |
- Mitiglinide
- Nateglinide
- Repaglinide
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GLP-1 agonists |
- Albiglutide†
- Dulaglutide
- Exenatide
- Liraglutide
- Lixisenatide
- Semaglutide†
- Taspoglutide†
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DPP-4 inhibitors/"gliptins" |
- Alogliptin
- Anagliptin
- Gemigliptin
- Linagliptin
- Omarigliptin
- Saxagliptin
- Sitagliptin
- Teneligliptin
- Vildagliptin
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Free fatty acid receptor 1 (GPR40) |
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Analogs/other insulins |
- fast-acting (Insulin aspart
- Insulin glulisine
- Insulin lispro)
- short-acting (Regular insulin)
- long-acting (Insulin detemir
- Insulin glargine
- NPH insulin)
- ultra-long-acting (Insulin degludec)
- inhalable (Exubera‡
- Afrezza)
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Other |
Aldose reductase inhibitors |
- Epalrestat
- Fidarestat§
- Ranirestat†
- Tolrestat‡
- Zenarestat§
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Alpha-glucosidase inhibitors |
- Acarbose
- Miglitol
- Voglibose
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Amylin analog |
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Sodium glucose transporter (SGLT2) inhibitors |
- Canagliflozin
- Dapagliflozin
- Empagliflozin
- Remogliflozin§
- Sergliflozin§
- Tofogliflozin†
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Other |
- Benfluorex‡
- Bromocriptine
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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UpToDate Contents
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English Journal
- Updates on Aldose Reductase Inhibitors for Management of Diabetic Complications and Non-diabetic Diseases.
- Grewal AS, Bhardwaj S, Pandita D, Lather V, Sekhon BS1.
- Mini reviews in medicinal chemistry.Mini Rev Med Chem.2015 Sep 9. [Epub ahead of print]
- Diabetes mellitus occurrence has been associated to the modification of the physiological levels of glucose and is often accompanied by several long-term complications, namely neuropathy, nephropathy, retinopathy, cataract, and cardiovascular. Aldose reductase (AR) is an enzyme of aldo-keto reductas
- PMID 26349493
- Amelioration of Bleomycin-induced Pulmonary Fibrosis of Rats by an Aldose Reductase Inhibitor, Epalrestat.
- Li X1, Shen Y1, Lu Y1, Yang J1.
- The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology.Korean J Physiol Pharmacol.2015 Sep;19(5):401-11. doi: 10.4196/kjpp.2015.19.5.401. Epub 2015 Aug 20.
- Aldose reductase (AR) is known to play a crucial role in the mediation of diabetic and cardiovascular complications. Recently, several studies have demonstrated that allergen-induced airway remodeling and ovalbumin-induced asthma is mediated by AR. Epalrestat is an aldose reductase inhibitor that is
- PMID 26330752
- Characterization of diabetic osteoarthritic cartilage and role of high glucose environment on chondrocyte activation: toward pathophysiological delineation of diabetes mellitus-related osteoarthritis.
- Laiguillon MC1, Courties A2, Houard X1, Auclair M1, Sautet A3, Capeau J1, Fève B1, Berenbaum F4, Sellam J2.
- Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society.Osteoarthritis Cartilage.2015 Sep;23(9):1513-22. doi: 10.1016/j.joca.2015.04.026. Epub 2015 May 15.
- OBJECTIVE: To examine the relationship between osteoarthritis (OA) and type 2 diabetes mellitus (DM).METHODS: OA cartilage from DM and non-DM patients undergoing knee replacement were stimulated by IL-1β for 24 h and release of interleukin-6 (IL-6) and prostaglandin E2 (PGE2) was measured. Primary
- PMID 25987541
Japanese Journal
- アルドース還元酵素阻害薬エパルレスタットによる薬物性肝障害の1例
- 藤瀬 幸,孝田 雅彦,加藤 順,徳永 志保,的野 智光,杉原 誉明,永原 天和,植木 賢,岡本 欣也,大山 賢治,岡野 淳一,前田 直人,桑本 聡史,村脇 義和
- 肝臓 52(6), 351-355, 2011
- 症例は60歳代の女性.平成21年2月頃から口渇・多飲・全身倦怠感が出現し,約3カ月で5 kgの体重減少を認めた.同年5月に空腹時血糖291 mg/dl ,HbA1c 12.6%と異常を認め,糖尿病および末梢神経障害の診断にてインスリン治療およびエパルレスタット150 mg/日と高コレステロール血症に対してロスバスタチンが開始された.7月中旬にAST 246 IU/L,ALT 375 IU/Lと肝機 …
- NAID 130000880383
- 糖尿病による血管障害の発症,予防における基礎的検討(特別講演I, 第154回名古屋市立大学医学会例会)
- 岡山 直司
- Nagoya medical journal 51(2), 107-114, 2010-09-01
- … The endothelial-neutrophil events activated by high glucose are also ameliorated by an aldose reductase inhibitor, epalrestat, antihypertensive egents, an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist, and a platelet aggregation inhibitor, cilostazol, but not by ticlopidine, sarpogrelate or aspirin. …
- NAID 110008147001
Related Links
- Find quality suppliers and manufacturers of Epalrestatfor price inquiry.where to buy Epalrestat.Also offer free database of Epalrestat including MSDS sheet(poisoning, toxicity, hazards and safety),chemical properties,Formula ...
- Selling Leads Epalrestat Nov 21, 2013 Product name: Epalrestat CAS:82159-09-9 Molecular formula:C15H13NO3S2 Molecular weight:319.39 Product description: Epalrestat is an aldose reductase inhibitor. Category: Chemicals | Antibiotic and Antimicrobial Agents
- 29 に吸収の極大を示す. (2)本品を乾燥し,赤外吸収スペクトル測定法の臭化カリウム錠剤法により測定 するとき,波数1748cm-1,1685cm-1,1564cm-1 及び1183cm-1 付近に吸収を認め る. 融点 222~227 類縁物質 本品0.020g をN,N ...
Related Pictures
★リンクテーブル★
[★]
- 英
- epalrestat
- 商
- エパタット、エパルドース、キナルドース、キネアドール、キネグルコ、キネスタット、キネダック、キネックス、キネルダー、キャルマック、サイロフト、モネダックス
- 関
- アルドース還元酵素阻害薬、糖尿病治療薬、薬理学
概念
適応
- 糖尿病性末梢神経障害に伴う自覚症状(しびれ感,疼痛),振動覚異常,心拍変動異常の改善(糖化ヘモグロビンが高値を示す場合)
重大な副作用
- 血小板減少があらわれることがあるので,このような症状があらわれた場合には,投与を中止すること.
- 2. 劇症肝炎,肝機能障害,黄疸,肝不全(頻度不明)
参考
- http://www.info.pmda.go.jp/go/pack/3999013F1282_1_01/3999013F1282_1_01?view=body
[★]
- 英
- aldose reductase inhibitor, ARI
- 関
- 糖尿病治療薬、薬理学、アルドースレダクターゼ阻害薬
- 糖尿病自体の治療ではなく、糖尿病合併症の治療薬である
- 糖尿病性末梢神経障害の治療に用いられる。
作用機序
- 高血糖では、細胞内で以下の反応が盛んに起こっている。ソルビトールが末梢神経障害の原因とされる。アルドース還元酵素阻害薬は細胞内のソルビトールの蓄積を妨げ、症状を改善する。
- グルコース-(アルドース還元酵素)→ソルビトール
アルドース還元酵素阻害薬