Opicapone (BIA 9-1067) reduces the ATP content of the cells (IC50: 98 μM). Opicapone is an effective third-generation catechol-O-methyltransferase inhibitor for the research of Parkinson's disease and motor fluctuations.

Opicapone decreases the mitochondrial membrane potential of the cells (IC50: 181 μM). Opicapone has a prolonged inhibitory effect on peripheral COMT, which extends the bioavailability of L-DOPA, without inducing toxicity. Incubation of human primary hepatocytes for 24 h with increasing concentrations of Ro 40-7592, OR-611 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) [1].

Opicapone inhibited rat peripheral COMT with ED50 values below 1.4 mg kg(-1) up to 6 h post-administration.?The effect was 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 were sustained up to 24 h post-administration.?Opicapone was 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].