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Chemical Structure| 130929-57-6 Chemical Structure| 130929-57-6

Structure of Entacapone
CAS No.: 130929-57-6

Chemical Structure| 130929-57-6

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Entacapone is a specific, potent and peripherally acting catechol-O-methyltransferase (COMT) inhibitor with IC50 of 151 nM for PD treatment.

Synonyms: OR-611

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Product Details of Entacapone

CAS No. :130929-57-6
Formula : C14H15N3O5
M.W : 305.29
SMILES Code : O=C(N(CC)CC)/C(C#N)=C/C1=CC([N+]([O-])=O)=C(O)C(O)=C1
Synonyms :
OR-611
MDL No. :MFCD00866580
InChI Key :JRURYQJSLYLRLN-BJMVGYQFSA-N
Pubchem ID :5281081

Safety of Entacapone

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335-H413
Precautionary Statements:P261-P273-P305+P351+P338

Isoform Comparison

Biological Activity

Target
  • Histone Methyltransferase

    COMT, IC50:151 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
Rat colon mucosal cells 200 μM 15 minutes Entacapone induced Cl- secretion in PD rat colon mediated by basolateral NKCC and apical membrane Cl- channels. PMC4375572
C2C12 cells 100 μM 48 hours Entacapone significantly reduced the Dex-induced upregulation of Atrogin-1 and Murf-1 protein levels and improved cell viability. PMC11663891
Rat colon longitudinal muscle cells 2 μM, 20 μM, 100 μM, 200 μM, 400 μM, 1000 μM Entacapone inhibited colon longitudinal muscle contraction in a dose-dependent manner with an EC50 of 200 μmol/L. PMC4375572

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Sprague-Dawley rats Healthy adult rats Oral 3 mg/kg Single dose, 24-hour observation To evaluate the pharmacokinetic properties of Entacapone-loaded nanostructured lipid carriers, the results showed that NLCs significantly increased AUC0–1, MRT, and t1/2, and reduced Kel, indicating prolonged drug action. PMC8986208
C57BL/6J mice Normal mice Oral 10, 50, or 200 mg/kg Once daily for 21 days To investigate the effects of entacapone on hippocampal neurogenesis in mice. Results showed that 50 and 200 mg/kg entacapone increased the exploration time for novel object recognition and significantly increased the numbers of Ki67-positive proliferating cells, doublecortin-positive immature neurons, and pCREB-positive cells. PMC8224137
Mice C57BL/6J mice Oral 50 mg/kg Once daily for 21 days Entacapone significantly increased proteins related to synaptic trafficking and plasticity, such as dynamin 1, synapsin I, and Munc18-1 in the hippocampus PMC7765944
C57BL/6J mice Mechanical ventilation-induced diaphragm dysfunction model Intraperitoneal injection 10 mg/kg Single dose, lasting 12 hours Entacapone significantly mitigated the decline in diaphragm strength caused by mechanical ventilation and reduced the upregulation of muscle atrophy markers Atrogin-1 and Murf-1. PMC11663891

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00192855 Schizophrenia COMPLETED 2025-10-06 Rambam medical center, Haifa, ... More >>31096, Israel Less <<
NCT00237263 Parkinson's Disease PHASE2 COMPLETED 2025-07-07 Novartis Pharmaceuticals, East... More >> Hanover, New Jersey, 07936, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 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

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2
The prepared working fluid is recommended to be prepared now and used up as soon as possible in a short period of time. The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1

References

[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.

 

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