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

Autor(es)

Ettcheto, Miren ^{[1, 2, 3, 4]} ; Busquets, Oriol ^{[1, 2, 3, 4, 5]} ; Sanchez-Lopez, Elena ^{[6, 7, 4]} ; Cano, Amanda ^{[6, 7, 4]} ; Manzine, Patricia R. ^{[1, 8, 3, 4, 5]} ; Verdaguer, Ester ^{[1, 4, 9]} ; Olloquequi, Jordi ^{[3, 10]} ; Auladell, Carme ^{[1, 4, 9]} ; Folch, Jaume ^{[1, 2]} ; Camins, Antoni ^{[1, 3, 4, 5, 10]}

Afiliação do(s) autor(es)

^[1] Biomed Res Networking Ctr Neurodegenerat Dis CIBE, Madrid - Spain

^[2] Univ Rovira & Virgili, Fac Med & Life Sci, Dept Biochem & Biotechnol, Reus - Spain

^[3] Univ Barcelona, Fac Pharm & Food Sci, Dept Pharmacol Toxicol & Therapeut Chem, Barcelona - Spain

^[4] Univ Barcelona, Inst Neurosci, Barcelona - Spain

^[5] Camins, Antoni, Univ Autonoma Chile, Fac Ciencias Salud, Inst Ciencias Biomed, Lab Cellular \& Mol Pathol, Talca, Chile.Ettcheto, Miren, Univ Barcelona, Fac Pharm & Food Sci, Dept Pharmacol Toxicol & Therapeut Chem, Barcelona - Spain

^[6] Univ Barcelona, Fac Pharm & Food Sci, Dept Pharm Pharmaceut Technol & Phys Chem, Barcelona - Spain

^[7] Univ Barcelona, Inst Nanosci & Nanotechnol IN2UB, Barcelona - Spain

^[8] Fed Univ Sao Carlos UFSCar, Dept Gerontol, Sao Carlos - Brazil

^[9] Univ Barcelona, Fac Biol, Dept Cellular Biol Physiol & Immunol, Barcelona - Spain

^[10] Univ Autonoma Chile, Fac Ciencias Salud, Inst Ciencias Biomed, Lab Cellular & Mol Pathol, Talca - Chile

• Tipo de documento: Artigo de Revisão
• Fonte: EXPERT OPINION ON DRUG DISCOVERY; v. 15, n. 9 MAY 2020.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 17/13224-5 - Estudo da via JNK1 como alvo seletivo para o tratamento de transtorno metabólico cognitivo: análise da proteína ADAM10
• Beneficiário: Patricia Regina Manzine Moralles
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 15/26084-1 - Avaliação da ADAM10 plaquetária em demências não-Alzheimer
• Beneficiário: Patricia Regina Manzine Moralles
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado