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

Autores da FMUP

• Patrício Manuel Vieira Araújo Soares Da Silva

  Autor

Participantes de fora da FMUP

• Jenner, P
• Rocha, JF
• Ferreira, JJ
• Rascol, O

Unidades de investigação

• Biomedicina

Abstract

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.

Keywords

• COMT; enzyme inhibition; levodopa; motor fluctuations; non-motor fluctuations; opicapone; Parkinson's disease; wearing-off