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].
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