Off-time Treatment Options for Parkinson’s Disease

Abstract

Motor fluctuations (MF) are deemed by patients with Parkinson's disease (PD) as the most troublesome disease feature resulting from the increasing impairment in responsiveness to dopaminergic drug treatments. MF are characterized by the loss of a stable response to levodopa over the nychthemeron with the reappearance of motor (and non-motor) parkinsonian clinical signs at various moments during the day and night. They normally appear after a few years of levodopa treatment and with a variable, though overall increasing severity, over the disease course. The armamentarium of first-line treatment options has widened in the last decade with new once-a-daily compounds,

Levodopa–Carbidopa–Entacapone Intestinal Gel in Advanced Parkinson Disease: A Multicenter Real-Life Experience

“…Despite considerable research, to date, no disease-modifying therapy for PD has been identified, 2 so treatment remains symptomatic, the primary aim being to replace lost dopamine, restore motor control, and minimize the time patients spend in the off state. 3…”

“…1 Despite considerable research, to date, no diseasemodifying therapy for PD has been identified, 2 so treatment remains symptomatic, the primary aim being to replace lost dopamine, restore motor control, and minimize the time patients spend in the off state. 3 Initial treatment of PD is generally with the "goldstandard" oral therapy, levodopa, which is converted to dopamine in the brain. However, commonly after a few years of treatment, levodopa becomes less effective in controlling symptoms, resulting in motor fluctuations (eg, end-of-dose wearing off, delayed on) and dyskinesias (involuntary movements).…”

“…American Journal of Therapeutics (2024) 31(3) www.americantherapeutics.comCopyright © 2024 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.…”

The Structural Characteristics of Compounds Interacting with the Amantadine-Sensitive Drug Transport System at the Inner Blood–Retinal Barrier

“…Moreover, based on the analysis of kinetic inhibition, pH-dependence, and L-carnitine sensitivity, the amantadine transport system is likely to be different from other putative cation transport systems of the inner BRB, which transport verapamil, clonidine, and propranolol [ 3 , 4 , 5 ]. Adamantane derivatives, such as amantadine and memantine, are known to exert neuroprotective effects by inhibiting N-methyl-D-aspartate (NMDA) receptors [ 6 , 7 , 8 , 9 ] and are used for the treatment of neurodegenerative disorders of the brain [ 10 , 11 , 12 , 13 ]. Previous studies showed that the overactivation of NMDA receptors caused damage to retinal ganglion cells [ 14 , 15 , 16 ] and it is considered a mechanism of retinal neurodegeneration under pathological conditions, such as glaucoma [ 17 , 18 , 19 ].…”

Patient Referral for Device‐Aided Therapies in Parkinson's Disease is Suboptimal; A Dutch Survey

“…1 The term DAT refers to deep brain stimulation (DBS), subcutaneous infusion of apomorphine and continuous infusion of levodopa/carbidopa intestinal gel with or without entacapone. 2 However, timely referral for DAT remains challenging. Not all eligible patients are referred to a specialized center in time, while others may be referred too early, both attributable to a lack of clear and objective referral criteria.…”