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Entacapone

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Chemical Structure| 130929-57-6 同义名 : OR-611
CAS号 : 130929-57-6
货号 : A102154
分子式 : C14H15N3O5
纯度 : 95%
分子量 : 305.286
MDL号 : MFCD00866580
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 35 mg/mL(114.65 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 2 mg/mL(6.55 mM)，配合低频超声，并调节pH至10
动物实验配方：

IP 2% DMSO+2% Tween80+30% PEG300+water 7 mg/mL clear

PO 0.5% CMC-Na 30 mg/mL suspension

生物活性
靶点

  • Histone Methyltransferase

    COMT, IC50:151 nM
描述 Catechol-O-methyltransferase (COMT) is an enzyme that inactivates dopamine and other catecholamines by O-methylation. Specifically, COMT plays a critical role in the inactivation and metabolism of dopamine and other catechol compounds. The enzyme reduces a catechol molecule in order to prevent genomic damage through DNA adduct formation or via oxygen radicals produced from the redox cycling of catechols[3]. Entacapone is a potent and specific peripheral catechol-O-methyltransferase (COMT) inhibitor with IC50 of 151 nM[4]. It has been shown to improve the clinical benefits of levodopa plus an aromatic L-amino acid decarboxylase inhibitor (AADC) when given to patients with Parkinson’s disease and end-of-dose deterioration in the response to levodopa (the ‘wearing off’ phenomenon)[5]. Entacapone treatment at 2 μM, 20 μM, 100 μM, 200 μM, 400 μM and 1000 M in PD model rats resulted in decreased longitudinal muscle contraction, from baseline (1233 ± 50.13 mg) to 1150 ± 64.96 mg, 859.9 ± 43.54 mg, 566.8 ± 92.6 mg, 450.6 ± 74.86 mg, 304.9 ± 53.7 mg and 307.98 ± 63.4 mg, respectively (n = 30).2A), which indicated that entacapone had an inhibitory effect on colon longitudinal muscle contraction with a dose-dependent pattern, by EC50 of 200 μM[6]. It was showed in double-blind study that Entacapone increased the area under the plasma concentration time-curve (0,12 h) of L-dopa to a similar extent at all doses of L-dopa/carbidopa (50/12.5 mg and 150/37.5 mg, or 100/10 mg and 100/25 mg, or 200/50 mg and 250/25 mg), that was by about 30-40% compared with placebo (P < 0.001, 95% CI 0.15, 0.40)[7].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.28mL

0.66mL

0.33mL

16.38mL

3.28mL

1.64mL

32.76mL

6.55mL

3.28mL
参考文献

[1]Di Giovanni S, Eleuteri S, et al. Entacapone and tolcapone, two catechol O-methyltransferase inhibitors, block fibril formation of alpha-synuclein and beta-amyloid and protect against amyloid-induced toxicity. J Biol Chem. 2010 May 14;285(20):14941-54.

[2]Piccini P, Brooks DJ, et al. The catechol-O-methyltransferase (COMT) inhibitor entacapone enhances the pharmacokinetic and clinical response to Sinemet CR in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2000 May;68(5):589-94.

[3]Funaki T, Onodera H, Ushiyama N, Tsukamoto Y, Tagami C, Fukazawa H, Kuruma I. The disposition of the tolcapone 3-O-methylated metabolite is affected by the route of administration in rats. J Pharm Pharmacol. 1994 Jul;46(7):571-4. doi: 10.1111/j.2042-7158.1994.tb03859.x. PMID: 7996385.

[4]De Santi C, Giulianotti PC, Pietrabissa A, Mosca F, Pacifici GM. Catechol-O-methyltransferase: variation in enzyme activity and inhibition by entacapone and tolcapone. Eur J Clin Pharmacol. 1998 May;54(3):215-9. doi: 10.1007/s002280050448. PMID: 9681662.

[5]Holm KJ, Spencer CM. Entacapone. A review of its use in Parkinson's disease. Drugs. 1999 Jul;58(1):159-77. doi: 10.2165/00003495-199958010-00017. PMID: 10439935.

[6]Li LS, Liu CZ, Xu JD, Zheng LF, Feng XY, Zhang Y, Zhu JX. Effect of entacapone on colon motility and ion transport in a rat model of Parkinson's disease. World J Gastroenterol. 2015 Mar 28;21(12):3509-18. doi: 10.3748/wjg.v21.i12.3509. PMID: 25834315; PMCID: PMC4375572.

[7]Heikkinen H, Varhe A, Laine T, Puttonen J, Kela M, Kaakkola S, Reinikainen K. Entacapone improves the availability of L-dopa in plasma by decreasing its peripheral metabolism independent of L-dopa/carbidopa dose. Br J Clin Pharmacol. 2002 Oct;54(4):363-71. doi: 10.1046/j.1365-2125.2002.01654.x. PMID: 12392583; PMCID: PMC1874436.