Pharmacokinetics of levodopa and personalized therapy in Parkinson’s disease

2020 ◽  
Vol 18 (5) ◽  
pp. 36-41
Author(s):  
A. A. TAPPAKHOV ◽  
◽  
T. E. POPOVA ◽  
T. G. GOVOROVA ◽  
Yu. I. KHABAROVA ◽  
...  

The article provides a review of the pharmacokinetics of levodopa and personalized therapy for Parkinson’s disease. We analyzed the methods used to prolong the action of levodopa using peripheral inhibitors of DOPA decarboxylase, catechol-O-methyltransferase inhibitors, and monoamine oxidase type B inhibitors. The influence of levodopa metabolites with their own biological activity in the possible progression of the disease is emphasized. The role of determining the concentration of levodopa in blood plasma is discussed, as well as the concept of «continuous dopamine stimulation» for the prevention and treatment of side effects of long-term levodopa therapy, such as drug dyskinesias, motor and non-motor fluctuations. The article also provides an overview of the modern forms of levodopa that are currently being investigated.

2021 ◽  
Vol 14 ◽  
Author(s):  
Mohammad Najim Uddin ◽  
Mohammad Injamul Hoq ◽  
Israt Jahan ◽  
Shafayet Ahmed Siddiqui ◽  
Chayan Dhar Clinton ◽  
...  

: Thymoquinone (TQ) is one of the leading phytochemicals, which is abundantly found in Nigella sativa L. seeds. TQ exhibited various biological effects such as antioxidant, anti-inflammatory, antimicrobial, and anti-tumoral in several pre-clinical studies. Parkinson's disease (PD) is a long-term neurodegenerative disease with movement difficulties, and the common feature of neurodegeneration in PD patients is caused by dopaminergic neural damage in the substantia nigra pars compacta. The neuroprotective activity of TQ has been studied in various neurological disorders. TQ-mediated neuroprotection against PD yet to be reported in a single frame; therefore, this review is intended to narrate the potentiality of TQ in the therapy of PD. TQ has been shown to protect against neurotoxins via amelioration of neuroinflammation, oxidative stress, apoptosis, thereby protects neurodegeneration in PD models. TQ could be an emerging therapeutic intervention in PD management, but mechanistic studies have been remained to be investigated to clarify its neuroprotective role.


Basal Ganglia ◽  
2017 ◽  
Vol 8 ◽  
pp. 22
Author(s):  
Daniel Pichler ◽  
Urban Fietzek ◽  
Franz Pfister ◽  
Ahmad Ahmadi ◽  
Felix Achilles ◽  
...  

2020 ◽  
Vol 10 (3) ◽  
pp. 176 ◽  
Author(s):  
Javier Pagonabarraga ◽  
José Matías Arbelo ◽  
Francisco Grandas ◽  
Maria-Rosario Luquin ◽  
Pablo Martínez Martín ◽  
...  

Safinamide is an approved drug for the treatment of motor fluctuations in Parkinson’s disease (PD). Scarce data are available on its use in clinical practice. A group of Spanish movement disorders specialists was convened to review the use of safinamide across different clinical scenarios that may guide neurologists in clinical practice. Eight specialists with recognized expertise in PD management elaborated the statements based on available evidence in the literature and on their clinical experience. The RAND/UCLA method was carried, with final conclusions accepted after a 2-round modified Delphi process. Higher level of agreement between panellists was reached for the following statements. Safinamide significantly improves mean daily OFF time without troublesome dyskinesias. Adjunctive treatment with safinamide is associated with motor improvements in patients with mid-to-late PD. The efficacy of safinamide on motor fluctuations is maintained at long-term, with no increase over time in dyskinesias severity. The clinical benefits of safinamide on pain and depression remain unclear. Safinamide presents a similar incidence of adverse events compared with placebo. The efficacy and safety of safinamide shown in the pivotal clinical trials are reproduced in clinical practice, with improvement of parkinsonian symptoms, decrease of daily OFF time, control of dyskinesias at the long term, and good tolerability and safety.


Author(s):  
Stefano Zoccolella ◽  
Paolo Lamberti ◽  
Giovanni Iliceto ◽  
Cosimo Diroma ◽  
Elio Armenise ◽  
...  

AbstractElevated plasma homocysteine (Hcy) concentrations are associated with Alzheimer's disease and vascular dementia. Several recent reports have indicated that L-dopa treatment is an acquired cause of hyperhomo-cysteinemia. Despite the fact that a large proportion of Parkinson's disease (PD) patients develop cognitive dysfunctions or dementia, particularly in the late stages of the illness and after long-term L-dopa treatment, the relationship between Hcy and dementia in PD has not been fully investigated. The aim of this study was to evaluate plasma Hcy levels in a group of L-dopa-treated PD patients with cognitive impairment and to elucidate a possible role of Hcy in the development of cognitive dysfunctions in PD. We compared Hcy, vitamin B


2021 ◽  
Author(s):  
Vladimir Kovalzon ◽  
Aleksandr Ambaryan ◽  
Aleksandr Revishchin ◽  
Galina Pavlova ◽  
Ekaterina Rybalkina ◽  
...  

Abstract We have previously shown that the aqueous extract of the Ulomoides dermestoides darking beetle (the Tenebrionidae family) biomass contains a powerful complex of antioxidant substances of protein and non-protein nature. Considering the crucial role of ROS in the development of neurodegeneration, we set out to test the biological activity of this extract in a mouse neurotoxic model of Parkinson's disease. The beetle extracts were administrated continuously with food and their effects on parkinsonism caused by twice injected defoliant paraquat to experimental mice was evaluated. The motor activity of the animals was analyzed in behavioral tests using a rotarod and a vertical pole. The number of tyrosine hydroxylase-immunopositive neurons in the ventral part of the substantia nigra of the midbrains of experimental and control mice was studied by immunohistochemistry. In the model in vitro system with SH-SY5Y human neuroblastoma, the effect of the extracts on cell proliferation was examined in the absence and presence of the neurotoxin MPP+. The isolation of biologically active substances from raw biomass using cavitation effects made it possible to obtain extracts with protective properties in the model of an early stage of Parkinson's disease used in this study.


Sign in / Sign up

Export Citation Format

Share Document