Opicapone 是一种每日一次的、有效的第三代儿茶酚-O-甲基转移酶e (COMT)抑制剂，用于帕金森病和运动波动治疗。Opicapone 降低细胞 ATP 含量，IC50为 98 μM。
CAS：923287-50-7
分子式：C15H10Cl2N4O6
分子量：413.17
纯度：98%
存储：Store at -20°C

Background:

Opicapone is a once-daily, potent third-generation catechol-O-methyltransferase (COMT) inhibitor for the treatment of Parkinson’s disease and motor fluctuations. Opicapone decreases the ATP content of the cells with IC50 of 98 μM. COMT[1]

Opicapone has a prolonged inhibitory effect on peripheral COMT, which extends the bioavailability of levodopa, without inducing toxicity. Opicapone decreases the ATP content of the cells with IC50 values of 98 μM. Incubation of human primary hepatocytes for 24 h with increasing concentrations of Tolcapone, entacapone or Opicapone resulted in a concentration-dependent decrease in the mitochondrial membrane potential of the cells, evaluated by the ratio JC-1 aggregates over JC-1 monomer (ratio Λex 544 Λem 590 over Λex 485 Λem 538). Opicapone decreases the mitochondrial membrane potential of the cells with IC50 of 181 μM[1].

Opicapone inhibits rat peripheral COMT with ED50 values below 1.4 mg/kg up to 6 h post-administration. The effect is sustained over the first 8 h and by 24 h COMT had not returned to control values. A single administration of Opicapone resulted in increased and sustained plasma levodopa levels with a concomitant reduction in 3-O-methyldopa from 2 h up to 24 h post-administration, while Tolcapone produced significant effects only at 2 h post-administration. The effects of Opicapone on brain catecholamines after levodopa administration are sustained up to 24 h post-administration. Opicapone is also the least potent compound in decreasing both the mitochondrial membrane potential and the ATP content in human primary hepatocytes after a 24 h incubation period[1].

[1]. BonifÁcio MJ, et al. Pharmacological profile of Opicapone, a third-generation nitrocatechol catechol-O-methyl transferase inhibitor, in the rat. Br J Pharmacol. 2015 Apr;172(7):1739-52. [2]. Ferreira JJ, et al. Opicapone as an adjunct to levodopa in patients with Parkinson’s disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial. Lancet Neurol. 2016 Feb;15(2):154-165.