Levodopa-induced Dyskinesia Research Articles

Sodium nitroprusside enhances stepping test performance and increases medium spiny neurons responsiveness to cortical inputs in a rat model of Levodopa-induced dyskinesias.

Levodopa (L-DOPA) is the classical gold standard treatment for Parkinson's disease. However, its chronic administration can lead to the development of L-DOPA-induced dyskinesias (LIDs). Dysregulation of the nitric oxide-cyclic guanosine monophosphate pathway in striatal networks has been linked to deficits in corticostriatal transmission in LIDs. This study investigated the effects of the nitric oxide (NO) donor sodium nitroprusside (SNP) on behavioural and electrophysiological outcomes in sham-operated and 6-hydroxydopamine-lesioned rats chronically treated with vehicle or L-DOPA, respectively. In sham-operated animals, systemic administration of SNP increased the spike probability of putative striatal medium spiny neurons (MSNs) in response to electrical stimulation of the primary motor cortex. In 6-hydroxydopamine-lesioned animals, SNP improved the stepping test performance without exacerbating abnormal involuntary movements. Additionally, SNP significantly increased the responsiveness of putative striatal MSNs in the dyskinetic striatum. These findings highlight the critical role of the NO signalling pathway in facilitating the responsiveness of striatal MSNs in both the intact and dyskinetic striata. The study suggests that SNP has the potential to enhance L-DOPA's effects in the stepping test without exacerbating abnormal involuntary movements, thereby offering new possibilities for optimizing Parkinson's disease therapy. In conclusion, this study highlights the involvement of the NO signalling pathway in the pathophysiology of LIDs.

Impulse control behaviors and apathy commonly co-occur in de novo Parkinson's disease and predict the incidence of levodopa-induced dyskinesia

ObjectiveImpulse control behaviors (ICBs) and apathy are believed to represent opposite motivational expressions of the same behavioral spectrum involving hypo- and hyperdopaminergic status, but this has been recently debated. Our study aims to estimate the co-occurrence of ICBs and apathy in early Parkinson's disease (PD) and to determine whether this complex neuropsychiatric condition is an important marker of PD prognoses. MethodsNeuropsychiatric symptoms, clinical data, neuroimaging results, and demographic data from de novo PD patients were obtained from the Parkinson's Progression Markers Initiative, a prospective, multicenter, observational cohort. The clinical characteristics of ICBs co-occurring with apathy and their prevalence were analyzed. We compared the prognoses of the different groups during the 8-year follow-up. Multivariate Cox regression analysis was conducted to predict the development of levodopa-induced dyskinesia (LID) using baseline neuropsychiatric symptoms. ResultsA total of 422 PD patients and 195 healthy controls (HCs) were included. In brief, 87 (20.6 %) de novo PD patients and 37 (19.0 %) HCs had ICBs at baseline. Among them, 23 (26.4 %) de novo PD patients and 3 (8.1 %) HCs had clinical symptoms of both ICBs and apathy. The ICBs and apathy group had more severe non-motor symptoms than the isolated ICBs group. Cox regression analysis demonstrated that the co-occurrence of ICBs and apathy was a risk factor for LID development (HR 2.229, 95 % CI 1.209 to 4.110, p = 0.010). ConclusionsCo-occurrence of ICBs and apathy is common in patients with early PD and may help to identify the risk of LID development.

Buspirone and Zolmitriptan Combination for Dyskinesia: A Randomized, Controlled, Crossover Study.

Preclinical evidence suggests that co-administration of the 5-HT1A agonist buspirone and the 5-HT1B/1D agonist zolmitriptan act synergistically to reduce dyskinesia to a greater extent than that achieved by either drug alone. Assess the therapeutic potential of a fixed-dose buspirone and zolmitriptan combination in Parkinson's disease (PD) patients with levodopa-induced dyskinesia. Single-center, randomized, placebo-controlled, two-way crossover study (NCT02439203) of a fixed-dose buspirone/zolmitriptan regimen (10/1.25 mg three times a day) in 30 patients with PD experiencing at least moderately disabling peak-effect dyskinesia. Seven days of treatment with buspirone/zolmitriptan added to levodopa significantly reduced dyskinesia as assessed by Abnormal Involuntary Movement Scale scores versus placebo (mean treatment effect vs. placebo: -4.2 [-6.1, -2.3]) without significantly worsening Unified Parkinson's Disease Rating Scale (UPDRS) Part III (ON) scores (mean treatment effect vs. placebo: 0.6 [-0.1, 1.3]). No serious adverse events were reported. In this proof-of-concept study, addition of buspirone/zolmitriptan to the patients' PD medication regimen significantly reduced dyskinesia severity without worsening motor function. © 2024 International Parkinson and Movement Disorder Society.

Learning Spatio-Temporal Radon Footprints for Assessment of Parkinson’s Dyskinesia

Parkinson’s disease is a severe neurodegenerative disorder that leads to loss of control over various motor and mental functions. Its progression can be limited with medication, particularly through the use of levodopa. However, prolonged administration of levodopa often results in disorders independent of those caused by the disease. The detection of these disorders is based on the clinical examination of patients, through different type of activities and tasks, using the Unified Dyskinesia Rating Scale (UDysRS). In the present work, our aim is to develop a state-of-the-art assessment system for levodopa-induced dyskinesia (LID) using the joint coordinate data of a human skeleton body depicted on videotaped activities related to UDysRS. For this reason, we combine a robust mathematical method for encoding action sequences known as Spatio-temporal Radon Footprints (SRF) with a Convolutional Neural Network (CNN), in order to estimate dyskinesia’s ratings for six body parts. We introduce two different methodological approaches: Global SRF-CNN and Local SRF-CNN, based on the set of skeletal points used in the encoding scheme. A comparison between these approaches reveals that Local SRF-CNN demonstrates better performance than the Global one. Finally, Local SRF-CNN outperforms the state-of-the-art technique, on both tasks, for UDysRS dyskinesia assessment, using joint coordinate data of the human body, achieving an overall performance in mean RMSE value of 0.6198 for Drinking task and 0.4885 for Communication, compared to 0.6575 and 0.5175, respectively. This illustrates the ability of the proposed machine learning system to successfully assess LID.

Continuous long-range measurement of tonic dopamine with advanced FSCV for pharmacodynamic analysis of levodopa-induced dyskinesia in Parkinson's disease.

Levodopa, a dopamine prodrug, alleviates the motor symptoms of Parkinson's disease (PD), but its chronic use gives rise to levodopa-induced dyskinesia (LID). However, it remains unclear whether levodopa pharmacodynamics is altered during the progressive onset of LID. Using in vivo fast-scan cyclic voltammetry and second-derivative-based background drift removal, we continuously measured tonic dopamine levels using high temporal resolution recording over 1-h. Increases to tonic dopamine levels following acute levodopa administration were slow and marginal within the naïve PD model. However, these levels increased faster and higher in the LID model. Furthermore, we identified a strong positive correlation of dyskinetic behavior with the rate of dopamine increase, but much less with its cumulative level, at each time point. Here, we identified the altered signature of striatal DA dynamics underlying LID in PD using an advanced FSCV technique that demonstrates the long-range dynamics of tonic dopamine following drug administration.

IRL790 modulated striatal D1 neurons synaptic plasticity ameliorating levodopa-induced dyskinesia in mouse.

Levodopa (L-dopa) therapy is the principal pharmacological treatment for Parkinson's disease (PD). Nevertheless, prolonged use of this drug may result in different involuntary movement symptoms caused by the medication, referred to as levodopa-induced dyskinesia (LID). LID is associated with changes in synaptic plasticity of the D1 medium spiny neurons (MSNs) located in the dorsal striatum (dStr). Within the striatum, the amount of Dopamine D3 receptor (D3R) is notably increased in LID, demonstrating colocalization with D1R expression in neurons, and the level of D3R expression is directly related to the intensity of LID. IRL 790, as a D3R antagonist, can ameliorate LID. This study aims to explore if IRL 790 improves LID by regulating the synaptic plasticity of D1+ MSNs in dStr. The electrophysiology and synaptic spine density of D1+ MSNs in dStr were recorded for sham mice, LID mice, and LID mice treated with IRL 790. The regulation of synaptic plasticity in LID D1+ MSNs by IRL 790 was analyzed. Behavioral tests were conducted to confirm the treatment effect of IRL 790 on LID. In LID D1+ MSNs, there was persistent abnormal LTP, absence of LTD, and an increase in spontaneous excitatory postsynaptic currents (sEPSCs). IRL 790 treatment restored normal LTP, LTD, and sEPSCs. Treatment with IRL 790 also restored the reduced dendritic spine density in D1+ MSNs of LID mice. IRL790 improved dyskinetic manifestations in LID mice. IRL790 ameliorates LID by regulating the synaptic structure and functional plasticity of striatal D1+ MSNs.

Parkinson's disease and levodopa-induced dyskinesias: a quantitative analysis through 99mTc-TRODAT-1 SPECT imaging of the brain.

To compare the dopamine transporter (DAT) density with other risk factors for L-DOPA-induced dyskinesia (LID) in patients with Parkinson's disease (PD), with and without LID. We evaluated 67 subjects: 44 patients with idiopathic PD of varying degrees of severity (PD group), and 23 healthy age-matched volunteers (control group). Among the 44 patients in the PD group, 29 were male and the following means were recorded at baseline: age, 59 ± 7 years; disease duration, 10 ± 6 years; Hoehn and Yahr (H&Y) stage, 2.16 ± 0.65; and Unified Parkinson's Disease Rating Scale part III (UPDRS III) score, 29.74 ± 17.79. All subjects underwent 99mTc-TRODAT-1 SPECT. We also calculated specific uptake ratios or binding potentials in the striatum. The DAT density in the ipsilateral and contralateral striata was lower in the PD group. The variables disease duration, L-DOPA dosage, doses per day, L-DOPA effect duration time, H&Y stage, and UPDRS III score explained the occurrence of LID. The DAT density in the ipsilateral striatum, contralateral striatum, and caudate nucleus was lower in the patients with LID than in those without. Our findings suggest that presynaptic dopaminergic denervation is associated with LID in individuals with PD.

The Parkinson's Story of a Neurologist with 32 Years of Experience on Parkinson's Disease.

As a neurologist who has followed up countless Parkinson's patients over the last 32 years of my fifty-year career; I denied diagnosing myself with Parkinson's disease (PD), although the seldom mild involuntary "twitches" that occurred in the thumb of my right hand over a two-year period, resembled Parkinson's disease tremor. However, when these involuntary contractions became persistent; considering its similarity to characteristic resting tremor in typical PD, the positive effect of dopaminergic medications, the development of levodopa-induced dyskinesias and other non-motor symptoms, it was clear that the PD diagnosis was accurate. This situation naturally caused me anxiety, and for a year and a half, I kept my diagnosis hidden from everyone except a few close relatives. However, with the encouragement of a psychiatrist friend, when I was able to share my condition with my loved ones, I felt a relative reduction in the burden I was carrying and consequently experienced emotional relief. I am still able to carry out my daily activities independently with a rather low dose of medication, and my PD symptoms do not attract noticeable attention.

Kaempferol ameliorated levodopa-induced dyskinesia in experimental rats: A role of brain monoamines, cFOS, FosB, Parkin, Pdyn, TH, and p-JNK

Kaempferol ameliorated levodopa-induced dyskinesia in experimental rats: A role of brain monoamines, cFOS, FosB, Parkin, Pdyn, TH, and p-JNK

Levodopa use in Australia: an analysis of Pharmaceutical Benefits Scheme 10% data

BackgroundLevodopa remains the mainstay of treatment of Parkinson’s disease, however, over time motor fluctuations and levodopa-induced dyskinesia develop, requiring add-on therapies to control emerging symptoms. To date, however, there is...

Targeting Striatal Glutamate and Phosphodiesterases to Control L-DOPA-Induced Dyskinesia.

A large body of work during the past several decades has been focused on therapeutic strategies to control L-DOPA-induced dyskinesias (LIDs), common motor complications of long-term L-DOPA therapy in Parkinson's disease (PD). Yet, LIDs remain a clinical challenge for the management of patients with advanced disease. Glutamatergic dysregulation of striatal projection neurons (SPNs) appears to be a key contributor to altered motor responses to L-DOPA. Targeting striatal hyperactivity at the glutamatergic neurotransmission level led to significant preclinical and clinical trials of a variety of antiglutamatergic agents. In fact, the only FDA-approved treatment for LIDs is amantadine, a drug with NMDAR antagonistic actions. Still, novel agents with improved pharmacological profiles are needed for LID therapy. Recently other therapeutic targets to reduce dysregulated SPN activity at the signal transduction level have emerged. In particular, mechanisms regulating the levels of cyclic nucleotides play a major role in the transduction of dopamine signals in SPNs. The phosphodiesterases (PDEs), a large family of enzymes that degrade cyclic nucleotides in a specific manner, are of special interest. We will review the research for antiglutamatergic and PDE inhibition strategies in view of the future development of novel LID therapies.

A video-atlas of levodopa-induced dyskinesia in Parkinson's disease: terminology matters.

Dyskinesia is a common complication of long-term levodopa therapy in patients with Parkinson's disease (PD), which often worsens the quality of life. It is usually dose-dependent and emerges possibly due to pulsatile stimulation of dopamine receptors. Delineating the pattern of dyskinesia is crucial for determining the most effective therapeutic approach, a task that often presents challenges for numerous neurologists. This article comprehensively describes various patterns of dyskinesia in PD patients and features video demonstration of some of the common forms of dyskinesia. We have used a real case scenario as an example to lead the discussion on the phenomenology, distinguishing features, and management of various types of dyskinesia. A comprehensive literature search was conducted in PubMed using "dyskinesia" as a keyword. The prototype case with videos highlights the differentiating features of dyskinesia along with the treatment strategies. A wide range of descriptive rubrics have been used for certain dyskinesia which are described in detail in this article. The newer types of dyskinesia associated with continuous dopaminergic stimulation in patients with advanced PD and their implications have been described. As there are distinct ways of managing various types of dyskinesia, understanding the phenomenology and chronology of dyskinesia is vital for the optimal management of dyskinetic PD patients. We suggest that dyskinesia should be classified broadly into peak-dose dyskinesia (PDD), biphasic dyskinesia (BD), and OFF-period dystonia. The occurrence of low-dose dyskinesia and complex dyskinesia of continuous dopaminergic treatments should be known to specialists and will require additional studies.

Microstructural and functional alterations of the ventral pallidum are associated with levodopa-induced dyskinesia in Parkinson's disease.

The ventral pallidum (VP) regulates involuntary movements, but it is unclear whether the VP regulates the abnormal involuntary movements in Parkinson's disease (PD) patients who have levodopa-induced dyskinesia (LID). To further understand the role of the VP in PD patients with LID (PD-LID), we explored the structural and functional characteristics of the VP in such patients using multimodal magnetic resonance imaging (MRI). Thirty-one PD-LID patients, 39 PD patients without LID (PD-nLID), and 28 healthy controls (HCs) underwent T1-weighted MRI, quantitative susceptibility mapping, multi-shell diffusion MRI, and resting-state functional MRI (rs-fMRI). Different measures characterizing the VP were obtained using a region-of-interest-based approach. The left VP in the PD-LID group showed significantly higher intracellular volume fraction (ICVF) and isotropic volume fraction (IsoVF) compared with the PD-nLID and HC groups. Rs-MRI revealed that, compared with the PD-nLID group, the PD-LID group in the medication 'off' state had higher functional connectivity (FC) between the left VP and the left anterior caudate, left middle frontal gyrus and left precentral gyrus, as well as between the right VP and the right posterior ventral putamen and right mediodorsal thalamus. In addition, the ICVF values of the left VP, the FC between the left VP and the left anterior caudate and left middle frontal gyrus were positively correlated with Unified Dyskinesia Rating Scale scores. Our multimodal imaging findings show that the microstructural changes of the VP (i.e., the higher ICVF and IsoVF) and the functional change in the ventral striatum-VP-mediodorsal thalamus-cortex network may be associated with pathophysiological mechanisms of PD-LID.

Dopamine-Depleted Dopamine Transporter Knockout (DDD) Mice: Dyskinesia with L-DOPA and Dopamine D1 Agonists.

L-DOPA is the mainstay of treatment for Parkinson's disease (PD). However, over time this drug can produce dyskinesia. A useful acute PD model for screening novel compounds for anti-parkinsonian and L-DOPA-induced dyskinesia (LID) are dopamine-depleted dopamine-transporter KO (DDD) mice. Treatment with α-methyl-para-tyrosine rapidly depletes their brain stores of DA and renders them akinetic. During sensitization in the open field (OF), their locomotion declines as vertical activities increase and upon encountering a wall they stand on one leg or tail and engage in climbing behavior termed "three-paw dyskinesia". We have hypothesized that L-DOPA induces a stereotypic activation of locomotion in DDD mice, where they are unable to alter the course of their locomotion, and upon encountering walls engage in "three-paw dyskinesia" as reflected in vertical counts or beam-breaks. The purpose of our studies was to identify a valid index of LID in DDD mice that met three criteria: (a) sensitization with repeated L-DOPA administration, (b) insensitivity to a change in the test context, and (c) stimulatory or inhibitory responses to dopamine D1 receptor agonists (5 mg/kg SKF81297; 5 and 10 mg/kg MLM55-38, a novel compound) and amantadine (45 mg/kg), respectively. Responses were compared between the OF and a circular maze (CM) that did not hinder locomotion. We found vertical counts and climbing were specific for testing in the OF, while oral stereotypies were sensitized to L-DOPA in both the OF and CM and responded to D1R agonists and amantadine. Hence, in DDD mice oral stereotypies should be used as an index of LID in screening compounds for PD.

Association of choroid plexus volume with motor symptoms and dopaminergic degeneration in Parkinson’s disease

BackgroundThe choroid plexus (CP) is involved in the clearance of harmful metabolites from the brain, as a part of the glymphatic system. This study aimed to investigate the association between...

Serum zinc deficiency is a potential risk factor for the occurrence of levodopa-induced dyskinesia in drug-naïve Parkinson's disease.

Since environmental factors, especially heavy metals, were highlighted in the pathogenesis of Parkinson's disease (PD), there are many epidemiologic studies regarding heavy metals and PD risk. However, longitudinal studies regarding the impacts of heavy metals on motor and nonmotor symptoms of PD are scarce. In the current study, we compared the serum levels of five heavy metals, such as zinc(Zn), copper(Cu), lead(Pb), mercury(Hg), and manganese(Mn), in 111 previously drug-naïve PD patients (n = 111) retrospectively. Among these 111 patients, 65 were PD patients without levodopa-induced dyskinesia (LID), while the other 46 had LID. We assembled clinical characteristics of PD and performed correlation analysis with heavy metal levels. At baseline, all subjects were examined with 18F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane positron emission tomography/computed tomography (FP-CIT PET/CT). We used Cox proportional hazards regression analysis for determining factors relevant to the time to LID development in PD subjects. Zn deficiency was significantly higher in the PD with LID group than in the PD without LID group (79.58 ± 12.28 versus 88.16 ± 15.15 μg/L). Lower serum Zn levels were significantly correlated with age of onset, levodopa equivalent daily dose (LEDD) at 3 months, and Korean version of the Mini-Mental State Examination (K-MMSE) scores (r = 0.16, p < 0.05, r = - 0.20, p < 0.01, r = 0.28, p < 0.01). Additionally, Zn deficiency was associated with a reduced time to LID development in the adjusted model (HR 0.978, 95% CI 0.956-0.999). This study suggests that serum Zn deficiency might be a risk factor for LID in drug-naïve PD patients.

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Evidence from epidemiological studies suggests an association between cigarette smoking and a low risk of Parkinson’s disease. Other data indicate a rapid worsening of the disease and an exacerbation of the disease after smoking cessation. To prevent the risk of Parkinson’s disease as the main component of cigarette smoke, nicotine is proposed as a alkaloid that has a fundamental role in the regulation of the behavior and activity of the striatum mediated by the dopaminergic system. Animal studies have also shown that nicotine can regulate dopamine transmission and reduce levodopa-induced dyskinesia. However, previous clinical trials have shown conflicting results regarding nicotine treatment. Epidemiological, preclinical, clinical updates and studies on dietary nicotine are presented. The suggestion to quit smoking for health reasons, as it reduces the risk of cancer and cardiovascular disease, should be accepted as an essential health procedure, however, in the case of Parkinson’s disease, a nicotine replacement supplement should be provided. Since small amounts of nicotine can lead to stimulation of a large portion of the brain’s nicotinic receptors, nicotine from other sources, such as less harmful advanced smoking devices, as well as diet, may be promising therapeutic agents to support motor function and protect against Parkinson’s disease.

Subthalamic deep brain stimulation improves vascular endothelial function in Parkinson's disease

ObjectivesVascular health (white matter change, vascular risk factor, angiogenesis, microvascular alteration) is associated with clinical progression or levodopa-induced dyskinesia in PD. Vascular endothelial function is known to reflect the earliest vascular change. While DBS can improve motor and non-motor symptoms, the effect of DBS on vascular endothelial function is unknown. Thus, we aimed to investigate whether DBS surgery could impact vascular endothelial function in PD. MethodA total of 20 PD patients were recruited. Vascular endothelial function was evaluated with flow-mediated dilation (FMD). FMD was investigated before and after one year of DBS surgery. ResultsFMD improved (6.01 ± 1.58 to 6.84 ± 1.57, p = 0.027). While the level of homocysteine slightly decreased (13.8 ± 4.1 to 13.0 ± 3.2, p = 0.05), there was no significant correlation between FMD changes and homocysteine levels (r = 0.42, p = 0.065). FMD change was associated with baseline age (r = −0.59, p = 0.006) but not with disease duration (p = 0.73), baseline UPDRS III (p = 0.81), change of UPDRS III and dyskinesia, and LEDD change (p = 0.94). Multivariate linear regression analysis revealed that only age (B = −0.139; p = 0.024) was significantly and inversely correlated with the change of FMD. ConclusionsWe found that STN-DBS improves vascular endothelial function in PD. Further studies are needed to clarify the exact pathogenesis and clinical implication of beneficial effects on vascular endothelial dysfunction in PD.

Antidyskinetic activity of new derivatives of inydazol-4,5-dicarbonic acid in a parkinsonism experimental model due to administration of 6-hydroxydopapine

BACKGROUND: Levodopa therapy currently remains the clinical method of choice for patients with Parkinsons disease. However, in the late stages of the disease, approximately 80% of patients receiving treatment developed levodopa-induced dyskinesia. The studied substances are derivatives of imidazole-4,5-dicarboxylic acid. Their pharmacological effect is produced due to interaction with the recognition site of NMDA receptor, which, together with their high efficiency, implies that they are safer than previously available drugs in this pharmacological group.&#x0D; AIM: To study the antidyskinetic effect of IEM2295 and IEM2296 derivatives of imidazole-4,5-dicarboxylic acid.&#x0D; MATERIALS AND METHODS: The model is based on the toxic effect of 6-hydroxydopamine on rat brain tissue. The first (control) group of rats received injections of only Levodopa and Benserazide, the second group received injections of Levodopa, Benserazide, and the test substance IEM2295, and the third group received injections of Levodopa, Benserazide and the test substance IEM2296. Each group was evaluated based on three criteria: motor function violations, limb dyskinesia, and axial and chewing dyskinesia. The severity of motor functions was graded on a scale of 0 to 4 points at 35, 70, 105, and 140 minutes after injection of the above substances, where 0 and 4 represent the absence and most pronounced degree of pathological movements, respectively.&#x0D; RESULTS: The result analysis showed that the greatest effect on reducing the severity of limb dyskinesia, axial dyskinesia, and chewing dyskinesia in rats was observed at 105 and 140 minutes after injections of the studied substances. Statistically significant differences between the control group and rats receiving injections of the studied substances were revealed at all the time points for limb dyskinesia; i.e., at 35, 105, and 140 minutes for axial dyskinesia and at 105 and 140 minutes for chewing dyskinesia.&#x0D; CONCLUSIONS: In the experimental model of parkinsonism, IEM2295 and IEM2296 show antiparkinsonian and antidyskinetic activity because they reduce the severity of motor function disorders in rats with levodopa-induced dyskinesia. The results indicate the prospects for continued development of these substances and further research for effective and safe antiparkinsonian agents among compounds of this class.

How does the method of formulation a drug affect its efficacy and safety, based on the comparison of modified and conventional release amantadine in the treatment of levodopa induced dyskinesia in patients with Parkinson's disease?

Background The choice of the appropriate method of drug production is determined mainly by the characteristics of the medicinal substances and excipients, the type of disease in which the drug is to be used and the expectations of patients. The appropriate method of drug production may be key importance for achieving clinically significant treatment effects. For this reason, an attempt has been made to evaluate modified and conventional release forms of amantadine for the treatment of levodopa-induced dyskinesias in patients with Parkinosn's disease. Methods The effect of two different forms of amantadine on the treatment of levodopa - induced dyskinesias in patients with Parkinson's disease was assessed through a systematic review of clinical trials following the PICOS regimen. The clinical efficacy of the treatment of levodopa-induced dyskinesias in patients with Parkinson's disease was assessed by a measure of the appropriate scale and the effect on the ON and OFF times. Results Although no studies were found directly comparing the use of amantadine ER with amantadine IR in this disease, in the studies of amantadine ER, the UDysRS score showed a significantly greater improvement in the treatment of dyskinesia in the study group compared to placebo. The amantadine IR studies did not show any significant effect on the treatment effects. Conclusions The choice of the method of producing a drug has a significant impact on the effects of treatment.