Opicapone

413.16900

413.17

Y5929UIJ5N

N04|N - Nervous system

150.66000

4.59830

1.80±0.1 g/cm3 (20 °C, 760 mmHg)

701.1±70.0 °C (760 mmHg)

minimal

|Warning|H228 (100%): Flammable solid [Danger Flammable solids]|P210, P240, P241, P280, and P370+P378|Aggregated GHS information provided by 2 companies from 2 notifications to the ECHA C&L Inventory.

Dyskinesia was the most serious adverse event frequently associated with opicapone administration. The reported incidence was 24% in a placebo-controlled trial (vs 8% with placebo) and 16% in the comparative trial (versus 4% with placebo and 8% with entacapone). Some other adverse events include dizziness, dry mouth, as well as constipation.

>99.7%

Opicapone is approved as an adjunctive therapy in adults with Parkinson’s disease and end-of-dose motor fluctuations whose symptoms cannot be stabilized on levodopa/dopa decarboxylase inhibitor combinations.|Ongentys is indicated as adjunctive therapy to preparations of levodopa/ DOPA decarboxylase inhibitors (DDCI) in adult patients with Parkinson's disease and end-of-dose motor fluctuations who cannot be stabilised on those combinations.Ongentys is indicated as adjunctive therapy to preparations of levodopa/ DOPA decarboxylase inhibitors (DDCI) in adult patients with Parkinson's disease and end-of-dose motor fluctuations who cannot be stabilised on those combinations.

Opicapone (OPC) is a powerful, reversible, and strictly peripheral third-generation catechol-O-methyltransferase inhibitor (COMT) inhibitor, which improves levodopa (L-Dopa) availability. It serves as adjunct therapy for L-Dopa treated patients with Parkinson's disease and motor fluctuations. Opicapone showed a significant (>90%) and long-lasting (>24 hours) COMT inhibition in healthy subjects after administration of a 50 mg dose. In 14- to 15-week, double-blind, multinational trials and in 1-year, open-label studies, opicapone demonstrated to be an effective and generally well tolerated adjunct therapy to L-Dopa plus a dopa decarboxylase inhibitor and other Parkinson disease therapy. During the double-blind phase, adjunctive opicapone 50 mg once daily provided significantly greater improvements in motor fluctuations than placebo, with these improvements noninferior to those with entacapone. These beneficial improvements in motor fluctuations with opicapone were maintained in patients who continued adjunctive opicapone during the extension studies, with patients who switched from placebo or entacapone to opicapone experiencing significant improvements in motor fluctuations during this year.

Compounds and drugs that inhibit or block the activity of CATECHOL O-METHYLTRANSFERASE enzymes. Drugs in this class are used in management of central nervous system disorders such as PARKINSON DISEASE. (See all compounds classified as Catechol O-Methyltransferase Inhibitors.)

Oral opicapone demonstrates linear, dose-dependent absorption. However, following simultaneous ingestion of a high-fat, high-calorie meal, the maximal plasma concentration is decreased. tmax of 1.0 h to 2.5 h after once-daily multiple-dose administration of up to 50 mg opicapone.|Opicapone is predominantly eliminated as metabolites in feces.|Approximately 30 L. One study showed small systemic accumulation after multiple-dosing.|In a pharmacokinetic trial, fter oral administration, the total body clearance of opicapone at a dose of 50 mg was 22 L/h, with an inter-subject variability of 45%.

Sulphation appears to be the main metabolic pathway for this drug. Other metabolic pathways include reduction, methylation, and glucuronidation. Opicapone undergoes N-oxide reduction to BIA 9-1079, an active metabolite, and this is the main metabolite in monkeys, and is less significant in rats and mice however. In humans, this metabolite is not detectable. However, human metabolism results in an an inactive metabolite _BIA 9-1103_, the result of 3-O-sulphation, and BIA 9-1104, the result of 4-O-methylation. BIA 9-1103 has been measured in mouse, rat and monkey samples, and BIA 9-1104 detected in negligible amounts in the mini-pig, rat and mouse samples, and therefore no unique human metabolites are present and all can be detected in at least one of the non-clinical species. Two have been examined with significance, BIA 9-1079 and BIA 9-1103.

1.58-4.50h Despite the short half-life, the observed half-life of opicapone-induced COMT inhibition in human red blood cells was 61.6 h (standard deviation [SD] = 37.6 h).

Opicapone is a peripheral, selective and reversible catechol-O-methyltransferase (COMT) inhibitor endowed with a high binding affinity (sub-picomolar) that results in a slow complex dissociation rate constant and long-term action (>24 hours) in vivo. In the presence of a DOPA decarboxylase inhibitor (DDCI), COMT acts as the primary metabolizing enzyme for levodopa, catalyzing the conversion to 3-O-methyldopa (3-OMD) in both the brain and periphery. In those taking levodopa and a peripheral DDCI, such as carbidopa or benserazide, opicapone augments levodopa plasma levels, thereby enhancing the efficacy of levodopa.

2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide

Human drugs -> Ongentys -> EMA Drug Category|Anti-Parkinson drugs -> Human pharmacotherapeutic group|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients