Opicapone

Opicapone (BIA 9-1067) is a potent third-generation catechol-O-methyltransferase (COMT) inhibitor for the research of Parkinson's disease and motor fluctuations. Opicapone decreases the ATP content of the cells with an IC₅₀ of 98 μM^[1]. IC50 & Target: COMT^[1] In Vitro: Opicapone has a prolonged inhibitory effect on peripheral COMT, which extends the bioavailability of L-DOPA, 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 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 λ_ex 544 λ_em 590 over λ_ex 485 λ_em 538). Opicapone decreases the mitochondrial membrane potential of the cells with IC₅₀ of 181 μM^[1]. In Vivo: 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 L-DOPA levels with a concomitant reduction in 3-OMD from 2 h up to 24 h post-administration, while Ro 40-7592 produces significant effects only at 2 h post-administration. The effects of Opicapone on brain catecholamines after L-DOPA 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].