The preclinical discovery and development of opicapone for the treatment of Parkinson’s disease

ABSTRACT

Introduction

Opicapone (OPC) is a well-established catechol-O-methyltransferase (COMT) inhibitor that is approved for the treatment of Parkinson’s disease (PD) associated with L-DOPA/L-amino acid decarboxylase inhibitor (DDI) therapy allowing for prolonged activity due to a more continuous supply of L-DOPA in the brain. Thus, OPC decreases fluctuation in L-DOPA plasma levels and favors more constant central dopaminergic receptor stimulation, thus improving PD symptomatology.

Areas covered

This review evaluates the preclinical development, pharmacology, pharmacokinetics and safety profile of OPC. Data was extracted from published preclinical and clinical studies published on PUBMED and SCOPUS (Search period: 2000–2019). Clinical and post-marketing data are also evaluated.

Expert opinion

OPC is a third generation COMT inhibitor with a novel structure. It has an efficacy and tolerability superior to its predecessors, tolcapone (TOL) and entacapone (ENT). It also provides a safe and simplified drug regimen that allows neurologists to individually adjust the existing daily administration of L-DOPA. OPC is indicated as an adjunctive therapy to L-DOPA/DDI in patients with PD and end-of-dose motor fluctuations who cannot be stabilized on those combinations.

KEYWORDS:

• Opicapone
• Parkinson’s disease
• dyskinesia
• entacapone
• tolcapone

Article highlights

• Opicapone is a third generation COMT inhibitor.

• Opicapone is administered once a day.

• Opicapone has high affinity to COMT as well as a slow dissociation constant and a prolonged duration of action.

• Opicapone is a better therapeutic agent than both ENT and TOL in patients with PD experiencing end-of-dose-fluctuations when used in combination with L-DOPA/DDI.

• Opicapone reduces ¨off ¨ time and increases ¨on¨ time.

• The therapeutic benefits of Opicapone 50mg are maintained without dose adjustment of L-DOPA/DDI for at least one year.

Acknowledgments

The authors thank WS Allyn MD, for reviewing the manuscript, providing corrections and his constructive criticism.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors are funded by the Spanish Ministry of Science and Innovation via grants [SAF2017-84283-R and CB06/05/0024] (CIBERNED), as well as European Regional Development Funds. The research team from the University of Barcelona and University Rovira i Virgili belongs to the Grup de Recerca en Envelliment i Neurodegeneració (Ref: 2017SGR625) from the Generalitat de Catalunya. PR Manzine is supported by grants [2015/26084-1 and 2017/13224-5] from the Sao Paulo Research Foundation (FAPESP) – Brazil.