scholarly journals Drug treatment of Parkinson's disease

2004 ◽  
Vol 6 (3) ◽  
pp. 315-322 ◽  

Parkinson's disease (PD) is a common neurodegenerative disease. While its cause remains elusive, much progress has been made regarding its treatment. Available drugs have a good symptomatic effect, but none has yet been shown to slow the progression of the disease in humans. The most efficacious drug is levodopa, but it remains unclear whether the symptomatic benefit is associated with neurotoxic effects and long-term deterioration. The long-term problem associated with levodopa is the appearance of dyskinesias, which is significantly delayed among patients treated with dopamine agonists as initial therapy. Less clear is the role of other drugs in PD, such as monoamine oxidase inhibitors (MAOIs), including selegiline and rasagiline, the putative N-meihyl-o-aspartaie (NMDA) receptor antagonists amantadine and memantine, and the muscarinic receptor blockers. All these may be used as initial therapy and delay the use of dopaminergic drugs, or can be added later to reduce specific symptoms (tremor or dyskinesias). Advanced PD is frequently associated with cognitive decline. To some extent, this can be helped by treatment with cholinesterase inhibitors such as rivastigmine. Similarly, hallucinations and delusions affect PD patients in the advanced stages of their disease. The use of classical neuroleptic drugs in these patients is contraindicated because of their extrapyramidal effects, but atypical drugs, and particularly clozapine, are very helpful. The big void in the therapy of PD lies in the more advanced stages. Several motor symptoms, like postural instability, dysphagia, and dysphonia, as well as dyskinesias, are poorly controlled by existing drugs. New therapies should also be developed against autonomic symptoms, particularly constipation.

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.


2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Eunju Shin ◽  
Elisabetta Tronci ◽  
Manolo Carta

L-DOPA, the most effective drug to treat motor symptoms of Parkinson's disease, causes abnormal involuntary movements, limiting its use in advanced stages of the disease. An increasing body of evidence points to the serotonin system as a key player in the appearance of L-DOPA-induced dyskinesia (LID). In fact, exogenously administered L-DOPA can be taken up by serotonin neurons, converted to dopamine and released as a false transmitter, contributing to pulsatile stimulation of striatal dopamine receptors. Accordingly, destruction of serotonin fibers or silencing serotonin neurons by serotonin agonists could counteract LID in animal models. Recent clinical work has also shown that serotonin neurons are present in the caudate/putamen of patients grafted with embryonic ventral mesencephalic cells, producing intense serotonin hyperinnervation. These patients experience graft-induced dyskinesia (GID), a type of dyskinesia phenotypically similar to the one induced by L-DOPA but independent from its administration. Interestingly, the 5-HT1Areceptor agonist buspirone has been shown to suppress GID in these patients, suggesting that serotonin neurons might be involved in the etiology of GID as for LID. In this paper we will discuss the experimental and clinical evidence supporting the involvement of the serotonin system in both LID and GID.


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


2017 ◽  
Vol 158 (51) ◽  
pp. 2023-2028
Author(s):  
József Attila Szász ◽  
Viorelia Constantin ◽  
Péter Alpár Fazakas ◽  
Eszter Blényesi ◽  
Levente Gábor Grieb ◽  
...  

Abstract: Introduction: Selective monoamine oxidase B inhibitors have an accurate place in therapeutical strategy of Parkinsons’s disease. In the early stages of the disease, especially in younger patients with milder symptoms, the introduction of levodopa substitution could be efficacious in delaying; in advanced stages they are mainly used to treat motor complications, as an adjunct to levodopa. Aim: The evaluation of therapeutical strategies used in the neurology clinics of Tirgu Mures County Emergency Clinical Hospital in order to define the role of monoamine oxidase B inhibitors. Method: This retrospective study includes all records of patients with Parkinson’s disease hospitalized between 1 January 2003 and 31 December 2016. From the 2194 reports we used data focusing on the therapeutic recommendations. Regarding disease duration, we divided the patients in two groups: less than or equal to 5 years and more than 5 years. Results: From the 1183 patients in first group, 243 received monoamine oxidase inhibitors: 12 as monotherapy, 52 together with dopamine agonists, in 61 cases combined with levodopa. In 118 cases monoamine oxidase inhibitors were combined with levodopa and dopamine agonists. From 582 cases whith Parkinson’s disease for more than 5 years, 195 received monoamine oxidase B inhibitors (selegiline: 10 cases, rasagiline: 185 cases). In 429 cases we did not find accurate data regarding disease duration (selegiline: 5 cases, rasagiline: 93 cases). Conclusion: The use of monoamine oxidase B inhibitors was similar to those found in literature. The treating physicians should utilise more confidently the available therapeutical combinations. Orv Hetil. 2017; 158(51): 2023–2028.


2019 ◽  
Vol 11 (3) ◽  
pp. 78-82 ◽  
Author(s):  
I. V. Miliukhina

The prevalence of depression in Parkinson's disease (PD) amounts to as much as 90%. The paper describes patients at different ages and with different durations of PD in its early and advanced stages and with various types of depressive disorder.The described clinical cases show that depression substantially worsens quality of life in a patient with PD and makes it difficult to choose antiparkinsonian therapy. Depression remains unrecognized on average in half of patients, while only a quarter of patients with identified depression receive timely treatment with antidepressants. PD complicated by depression is characterized by a faster progression and more significantly impaired quality of life and cognitive status than PD without affective disorders. Patients with PD and depressive disorder are characterized by an insufficient response to standard doses of antiparkinsonian drugs, which often leads to an irrational increase in the dose of dopaminergic drugs and to the development of complications.Difficulties in choosing an antidepressant for PD are associated with the development of a complex multicomponent neurotransmitter imbalance in this disease. The prescription of multimodal antidepressants can solve this problem.It is necessary to timely detect and correct depression in patients with PD using the currently available drugs and nonpharmacological methods (psychotherapy and physical rehabilitation). 


2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Antonio Daniele ◽  
Francesco Panza ◽  
Antonio Greco ◽  
Giancarlo Logroscino ◽  
Davide Seripa

At present, patients with advanced Parkinson’s disease (PD) are unsatisfactorily controlled by currently used anti-Parkinsonian dopaminergic drugs. Various studies suggest that therapeutic strategies based on nondopaminergic drugs might be helpful in PD. Zolpidem, an imidazopyridine widely used as sleep inducer, shows high affinity only forGABAAreceptors containing theα-1 subunit and facilitates GABAergic neurotransmission through a positive allosteric modulation ofGABAAreceptors. Various observations, although preliminary, consistently suggest that in PD patients zolpidem may induce beneficial (and sometimes remarkable) effects on motor symptoms even after single doses and may also improve dyskinesias. Since a high density of zolpidem binding sites is in the two main output structures of the basal ganglia which are abnormally overactive in PD (internal globus pallidus, GPi, and substantia nigra pars reticulata, SNr), it was hypothesized that in PD patients zolpidem may induce throughGABAAreceptors an inhibition of GPi and SNr (and, possibly, of the subthalamic nucleus also), resulting in an increased activity of motor cortical areas (such as supplementary motor area), which may give rise to improvement of motor symptoms of PD. Randomized clinical trials are needed in order to assess the efficacy, safety, and tolerability of zolpidem in treating motor symptoms of PD.


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.


Author(s):  
A. Rascol ◽  
J.L. Montastruc ◽  
O. Rascol

ABSTRACTThe long term consequences of the use of a dopamine agonist, bromocriptine, in the treatment of Parkinson’s disease are reported. In a first study in 82 patients showing late side effects of levodopa, bromocriptine permitted a significant decrease of the gastro-intestinal adverse effects. In contrast, no significant improvement of end of dose deterioration from levodopa was noted. In cases where levodopa had ceased to be active, bromocriptine produced an improvement in the clinical state. The drug was ineffective in the very advanced stages of the disease or in the cases of dyskinesias without “on-off” effects. Bromocriptine did not significantly improve freezing or “on-off” effects, but reduced other side effects of levodopa, in particular dystonia. In a second group of 29 patients who had never received levodopa treatment, bromocriptine was shown to be very effective as a first treatment of the disease. The most important finding was the absence of long term side effects similar to those usually observed under levodopa: in this group and in comparison with 38 patients taking levodopa, dyskinesia, dystonia, oscillations in performance and especially “on-off” effects were not noted. However, a partial loss of efficacy of bromocriptine was observed in 27% of cases. In a third group of 10 patients, bromocriptine introduced according to a low and slow protocol was found to be active in a limited number of patients only.


2015 ◽  
Vol 26 (2) ◽  
pp. 109-120 ◽  
Author(s):  
Larissa R. Arndt ◽  
Günter Esser ◽  
Sebastian Weirich ◽  
Henriette Oelsner ◽  
Georg Ebersbach ◽  
...  

We examined face memory deficits in patients with Idiopathic Parkinson’s disease (IPD) with specific regard to the moderating role of sex and the different memory processes involved. We tested short- and long-term face recognition memory in 18 nonclinical participants and 18 IPD-patients matched for sex, education and age. We varied the duration of item presentation (1, 5, 10s), the time of testing (immediately, 1hr, 24hrs) and the possibility to re-encode items. In accordance with earlier studies, we report face memory deficits in IPD. Moreover, our findings indicate that sex and encoding conditions may be important moderator variables. In contrast to healthy individuals, IPD-patients cannot gain from increasing duration of presentation. Furthermore, our results suggest that IPD leads to face memory deficits in women, only.


2011 ◽  
Vol 6 (3) ◽  
pp. 156 ◽  
Author(s):  
Kar in Busk ◽  
Anders Johansson ◽  
Dag Nyholm ◽  
◽  
◽  
...  

Continuous dopaminergic stimulation (CDS) is important for symptom control in advanced stages of Parkinson’s disease (PD). The most efficacious approaches are pump treatments with dopaminergic drugs: subcutaneous infusion of the dopamine receptor agonist apomorphine and intestinal infusion of levodopa/carbidopa gel. Both methods decrease motor fluctuations in long-term follow-ups, including parkinsonian and dyskinetic states, when compared to conventional optimised oral therapy. Also non-motor symptoms may be improved. Adverse drug reactions are usually less pronounced although high levodopa doses, which are common with levodopa/carbidopa infusion, may cause hyperhomocysteinaemia and cobalamin deficiency. Technical complications are specific for each infusion strategy. Formation of subcutaneous nodules is the most common problem with apomorphine infusion. Dislocation of the intestinal tube is the most common problem with levodopa/carbidopa infusion. Both pump treatments may be used for 24-hour infusion in selected patients. The long-term experience is reviewed. To conclude, CDS pump treatments may be successfully used for several years in advanced PD.


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