Opicapone

923287-50-7

C15H10Cl2N4O6

DMSO : 100 mg/mL (242.03 mM; Need ultrasonic); H2O : < 0.1 mg/mL (insoluble)

Neuronal Signaling; Metabolic Enzyme/Protease

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 uM. IC50 & Target: COMT^[1] In Vitro: 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 uM. 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 lambda_ex 544 lambda_em 590 over lambda_ex 485 lambda_em 538). Opicapone decreases the mitochondrial membrane potential of the cells with IC₅₀ of 181 uM^[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 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].