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].
Entacapone/恩他卡朋 细胞实验
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.
World J Gastroenterol. 2015 Mar 28;21(12):3509-18.
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.
Front Physiol. 2024 Dec 9;15:1483594.
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.
World J Gastroenterol. 2015 Mar 28;21(12):3509-18.
Entacapone/恩他卡朋 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
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.
Front Physiol. 2024 Dec 9;15:1483594.
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.
Neural Regen Res. 2021 Jun;16(6):1005-1110
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.
Drug Deliv. 2022 Dec;29(1):1112-1121
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
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