Opicapone, a Novel Catechol-O-methyl Transferase Inhibitor, for Treatment of Parkinson’s Disease “Off” Episodes

Abstract

Parkinson’s Disease (PD) is a common neurodegenerative disorder and the leading cause of disability. It causes significant morbidity and disability through a plethora of symptoms, including movement disorders, sleep disturbances, and cognitive and psychiatric symptoms. The traditional pathogenesis theory of PD involves the loss of dopaminergic neurons in the substantia nigra (SN). Classically, treatment is pursued with an assortment of medications that are directed at overcoming this deficiency with levodopa being central to most treatment plans. Patients taking levodopa tend to experience “off episodes” with decreasing medication levels, causing large fluctuations in their symptoms. These off episodes are disturbing and a source of morbidity for these patients. Opicapone is a novel, peripherally acting Catechol-O-methyl transferase (COMT) inhibitor that is used as adjunctive therapy to carbidopa/levodopa for treatment and prevention of “off episodes.” It has been approved for use as an adjunct to levodopa since 2016 in Europe and has recently (April 2020) gained FDA approval for use in the USA. By inhibiting COMT, opicapone slows levodopa metabolism and increases its availability. Several clinical studies demonstrated significant improvement in treatment efficacy and reduction in duration of “off episodes.” The main side effect demonstrated was dyskinesia, mostly with the 100mg dose, which is higher than the approved, effective dose of 50mg. Post-marketing surveillance and analysis are required to further elucidate its safety profile and contribute to patient selection. This paper reviews the seminal and latest evidence in the treatment of PD “off episodes” with the novel drug Opicapone, including efficacy, safety, and clinical indications.

Therapeutic Potential of Dopamine and Related Drugs as Anti-Inflammatories and Antioxidants in Neuronal and Non-Neuronal Pathologies

“…Likewise, the most common COMT inhibitors are entacapone, opicapone, and tolcapone. They inhibit the COMT enzyme and are frequently used in the treatment of Parkinson’s disease as an adjunct to levodopa/carbidopa medication [ 95 , 96 , 97 ]. Many Parkinson’s disease patients treated with levodopa plus carbidopa experience motor complications over time; when COMT inhibitors are administered, plasma levodopa levels are increased and maintained, resulting in more consistent dopaminergic stimulation, leading to further reduction of the manifestations of parkinsonian syndrome [ 98 ].…”

Drug Development for Alzheimer’s and Parkinson’s Disease: Where Do We Go Now?

“…In addition to L-DOPA, other therapeutic approaches involve the use of selective MAO-B inhibitors (rasagiline, selegiline, safinamide), COMT inhibitors (entacapone, tolcapone and opicapone) [136,137], or the agonists of postsynaptic DA receptors (pramipexole, ropinirole, apomorphine) (Figure 7) [138,139]. Due to their pivotal role in neurotransmi er catabolism and their affinity for specific neurotransmi ers, MAOs are considered a ractive drug targets in the treatment of depression and NDs [140,141].…”

“…In addition to L-DOPA, other therapeutic approaches involve the use of selective MAO-B inhibitors (rasagiline, selegiline, safinamide), COMT inhibitors (entacapone, tolcapone and opicapone) [ 136 , 137 ], or the agonists of postsynaptic DA receptors (pramipexole, ropinirole, apomorphine) ( Figure 7 ) [ 138 , 139 ].…”

Drug Development for Alzheimer’s and Parkinson’s Disease: Where Do We Go Now?

“…In addition to L-DOPA, other therapeutic approaches involve the use of selective MAO-B inhibitors (rasagiline, selegiline, safinamide), COMT inhibitors (entacapone, tolcapone and opicapone) [134,135], or agonists of postsynaptic DA receptors (pramipexole, ropinirole, apomorphine) (Figure 7) [136,137]. Due to their pivotal role in neurotransmitter catabolism and their affinity for specific neurotransmitters, MAOs are considered attractive drug targets in the treatment of depression and NDs [138,139].…”