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.

• Authors: Miren Ettcheto, Oriol Busquets, Elena Sánchez-Lopez, Amanda Cano, Patricia R Manzine, Ester Verdaguer, Jordi Olloquequi, Carme Auladell, Jaume Folch, Antoni Camins
• Journal: Expert opinion on drug discovery (Expert Opin Drug Discov) Vol. 15 Issue 9 Pg. 993-1004 (09 2020) ISSN: 1746-045X [Electronic] England
• PMID: 32450711 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antiparkinson Agents
• Catechol O-Methyltransferase Inhibitors
• Oxadiazoles
• Levodopa
• opicapone

Topics

• Animals
• Antiparkinson Agents (administration & dosage, adverse effects, pharmacology)
• Catechol O-Methyltransferase Inhibitors (administration & dosage, adverse effects, pharmacology)
• Drug Development
• Drug Evaluation, Preclinical
• Humans
• Levodopa (metabolism)
• Oxadiazoles (administration & dosage, adverse effects, pharmacology)
• Parkinson Disease (drug therapy, physiopathology)