Opicapone enhances the reversal of MPTP-induced Parkinson-like syndrome by levodopa in cynomolgus monkeys

Bonifácio, Maria João; Sousa, Filipa; Soares‐da‐Silva, Patrício

doi:10.1016/j.ejphar.2020.173742

Cited by 5 publications

(1 citation statement)

References 35 publications

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“…Oral administration of opicapone with levodopa to rats resulted in a sustained increase in brain levodopa levels that was evident 24 hours after drug administration. Similar results were seen in the cynomolgus monkey, where administration of adjunct opicapone to levodopa/benserazide increased levodopa systemic exposure by 2-fold without changing C max values [60,61] and reduced both 3-OMD exposure and C max values by up to 7-fold [60,61]. These changes were accompanied by an up to ~85% reduction in erythrocyte COMT activity [60,61] and translated into an improvement in motor function in MPTP treated parkinsonian primates [61].…”

Section: Opicapone -Experimental Biochemistry and Pharmacologysupporting

confidence: 69%

Redefining the strategy for the use of COMT inhibitors in Parkinson’s disease: the role of opicapone

Jenner

Rocha

Ferreira

et al. 2021

Expert Review of Neurotherapeutics

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Introduction: Levodopa remains the gold-standard Parkinson's disease (PD) treatment, but the inevitable development of motor complications has led to intense activity in pursuit of its optimal delivery. Areas covered: Peripheral inhibition of dopa-decarboxylase has long been considered an essential component of levodopa treatment at every stage of illness. In contrast, only relatively recently have catechol-O-methyltransferase (COMT) inhibitors been utilized to block the other major pathway of degradation and optimize levodopa delivery to the brain. First and second-generation COMT inhibitors were deficient because of toxicity, sub-optimal pharmacokinetics or a short duration of effect. As such, they have only been employed once 'wearing-off' has developed. However, the third-generation COMT inhibitor, opicapone has overcome these difficulties and exhibits long-lasting enzyme inhibition without the toxicity observed with previous generations of COMT inhibitors. In clinical trials and real-world PD studies opicapone improves the levodopa plasma profile and results in a significant improvement in ON time in 'fluctuating' disease, but it has not yet been included in the algorithm for early treatment. Expert opinion: This review argues for a shift in the positioning of COMT inhibition with opicapone in the PD algorithm and lays out a pathway for proving its effectiveness in early disease.

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