Levodopa-induced Dyskinesia In Patients Research Articles

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.

Levodopa-Induced Dyskinesia in Parkinson's Disease: Pathogenesis and Emerging Treatment Strategies.

The most commonly used treatment for Parkinson's disease (PD) is levodopa, prescribed in conjunction with carbidopa. Virtually all patients with PD undergo dopamine replacement therapy using levodopa during the course of the disease's progression. However, despite the fact that levodopa is the "gold standard" in PD treatments and has the ability to significantly alleviate PD symptoms, it comes with side effects in advanced PD. Levodopa replacement therapy remains the current clinical treatment of choice for Parkinson's patients, but approximately 80% of the treated PD patients develop levodopa-induced dyskinesia (LID) in the advanced stages of the disease. A better understanding of the pathological mechanisms of LID and possible means of improvement would significantly improve the outcome of PD patients, reduce the complexity of medication use, and lower adverse effects, thus, improving the quality of life of patients and prolonging their life cycle. This review assesses the recent advancements in understanding the underlying mechanisms of LID and the therapeutic management options available after the emergence of LID in patients. We summarized the pathogenesis and the new treatments for LID-related PD and concluded that targeting pathways other than the dopaminergic pathway to treat LID has become a new possibility, and, currently, amantadine, drugs targeting 5-hydroxytryptamine receptors, and surgery for PD can target the Parkinson's symptoms caused by LID.

Advanced radiological investigation of levodopa- induced dyskinesia in Parkinson’s disease patients: assessment of blood brain barrier function

Background: The purpose of this study is to explore changes in blood-brain barrier (BBB) function and volumetry associated with Parkinson’s disease (PD) levodopa-induced-dyskinesia (LID). Methods: Twenty-six PD patients [matched pairs, 13 with LID (LID+) and 13 without (LID-)], performed high resolution 3D FSPGR MRI, applying a novel methodology developed for calculating delayed- enhancement-subtraction-maps, representing BBB function. Segmentation software calculated volumes of pre-determined brain structures and the mean BBB function was calculated for each structure. Comparisons between the LID+ and LID- paired patients and within patient, between the more and less affected hemisphere (MAH, LAH) and correlation tests with lateralized UPDRS motor scores were performed. Results: There were no significant differences in volumetric or BBB map characteristics between the matched LID+ and LID- patients regarding most brain areas except for the inferior parietal cortex (IPC) of the MAH that displayed a higher BBB disruption in LID+ vs. LID- patients. A positive correlation was found with the motor score of the side contralateral to the MAH(r = 0.58, p<0.038) among the LID+ patients. Conclusions: We demonstrated an association between slight BBB disruption in the IPC and LID in patients with PD using a new MRI methodology. As currently there is no known straightforward biological explanation for this positive finding, it might be genuine and novel, or spurious. Further studies to explore BBB functioning in the various stages of PD and its motor complications are needed, as well as further investigation of the IPC clinical importance and correction for epiphenomenon.

Premorbid Educational Attainment and Long-Term Motor Prognosis in Parkinson's Disease.

Premorbid educational attainment is a well-known proxy of reserve, not only with regard to cognition, but also to motor symptoms. In the present study, we investigated the relationship between educational attainment and long-term motor prognosis in patients with Parkinson's disease (PD). We analyzed 466 patients with de novo PD without dementia who underwent dopamine transporter (DAT) scans and were followed up more than 2 years. Patients were divided into three groups: low education (years-of-education ≤6, n = 125), intermediate education (6 <years-of-education < 12, n = 108), and high education (years-of-education ≥12, n = 233). The effects of educational attainment on the development of levodopa-induced dyskinesia (LID), wearing-off, and freezing-of-gait, and longitudinal increase in levodopa-equivalent doses (LEDs) were assessed. Multiple regression analysis showed that higher education was associated with milder parkinsonian symptoms after adjusting for DAT availability in the posterior putamen. Survival analysis showed that the rate of LID was significantly lower in the high education group than in the low education group (HR = 0.565, p = 0.010). A linear mixed model showed that the high education group had lower LED than the low education group until a period of 30 months; however, this difference in LED was not observed thereafter. The present study demonstrated that premorbid educational attainment has protective effects on the development of LID in patients with PD and has sparing effects on LED during the early treatment period. These results suggest that high educational attainment has a beneficial effect on motor outcomes in patients with PD.

Amantadine treatment and delayed onset of levodopa-induced dyskinesia in patients with early Parkinson's disease.

Levodopa-induced dyskinesia (LID) is a common motor complication in patients with Parkinson's disease (PD). Although amantadine is indicated for LID treatment, it is uncertain whether early treatment with amantadine reduces the risk of LID in patients with PD. We aimed to evaluate the association between amantadine treatment and LID onset in patients with early-stage PD. This was a hospital-based retrospective cohort study that used electronic medical records from January 1, 2009 to October 31, 2016. The effect of amantadine on LID onset was compared with those of anticholinergics and monoamine oxidase type B inhibitors in patients with PD. Propensity-score weighting and landmark analysis were used to reduce potential confounding. The time to LID onset was analyzed using Cox models. Sensitivity analyses were performed to determine the robustness of the results. The analyses included 807, 661, and 518 patients at 6-, 12-, and 18-month landmark points, respectively. Amantadine use was associated with delayed LID onset in the 6- and 12-month landmark analyses, with adjusted hazard ratios of 0.65 (95% confidence interval [CI] = 0.49-0.86) and 0.64 (95% CI = 0.47-0.88), respectively. Sensitivity analysis findings were comparable to those of the main analysis. Early treatment with amantadine may delay LID onset more than treatment with other symptomatic agents. Further studies are needed to elucidate the mechanism of amantadine in LID onset delay and to validate our findings.

The Influence of ADORA2A on Levodopa-Induced Dyskinesia.

Dopamine deficiency causes Parkinson's disease (PD), and on treatment, levodopa is the gold standard. Various drug-metabolizing enzymes and drug receptors are believed to be involved in prompting dyskinesias due to the extended usage of levodopa. Shreds of evidence in genomic studies have presented that ADORA2A receptor antagonism has beneficial outcomes to avoid these drug-induced side effects. The aim of this study was to study the polymorphisms of rs2298383, rs35060421, and rs5751876 in the ADORA2A in patients diagnosed as PD and describe their possible relationships with levodopa-induced dyskinesias (LID). One-hundred and seventy-two patients were recruited and separated as the study and the control group. DNA was achieved from peripheral venous blood, high resolution melting analysis, and reverse-transcriptase PCR was performed. The allele differences among the groups were not statistically significant. Although it was not statistically significant, the rs35060421 allele was observed to repeat more frequently. However, we did not find an association between such polymorphisms of ADORA2A and LID. Although this result showed that a higher sample number might produce different results as possible, current results in the Turkish sample indicated that these alleles of ADORA2A might not be related to LID in patients.

Metabolic Profile in Plasma AND CSF of LEVODOPA-induced Dyskinesia in Parkinson's Disease: Focus on Neuroinflammation.

The existence of few biomarkers and the lack of a better understanding of the pathophysiology of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) require new approaches, as the metabolomic analysis, for discoveries. We aimed to identify a metabolic profile associated with LID in patients with PD in an original cohort and to confirm the results in an external cohort (BioFIND). In the original cohort, plasma and CSF were collected from 20 healthy controls, 23 patients with PD without LID, and 24 patients with PD with LID. LC-MS/MS and metabolomics data analysis were used to perform untargeted metabolomics. Untargeted metabolomics data from the BioFIND cohort were analyzed. We identified a metabolic profile associated with LID in PD, composed of multiple metabolic pathways. In particular, the dysregulation of the glycosphingolipid metabolic pathway was more related to LID and was strongly associated with the severity of dyskinetic movements. Furthermore, bile acid biosynthesis metabolites simultaneously found in plasma and CSF have distinguished patients with LID from other participants. Data from the BioFIND cohort confirmed dysregulation in plasma metabolites from the bile acid biosynthesis pathway. There is a distinct metabolic profile associated with LID in PD, both in plasma and CSF, which may be associated with the dysregulation of lipid metabolism and neuroinflammation.

The Relationship Between Electrical Energy Delivered by Deep Brain Stimulation and Levodopa-Induced Dyskinesias in Parkinson's Disease: A Retrospective Preliminary Analysis.

Background: Adaptive Deep Brain Stimulation (aDBS) is now considered as a new feasible and effective paradigm to deliver DBS to patients with Parkinson's disease (PD) in such a way that not only stimulation is personalized and finely tuned to the instantaneous patient's state, but also motor improvement is obtained with a lower amount of energy transferred to the tissue. Amplitude-controlled aDBS was shown to significantly decrease the amplitude-driven total electrical energy delivered to the tissue (aTEED), an objective measure of the amount of energy transferred by DBS amplitude to the patient's brain. However, there is no direct evidence of a relationship between aTEED and the occurrence of DBS-related adverse events in humans.Objective: In this work, we investigated the correlation of aTEED with the occurrence of levodopa-induced dyskinesias pooling all the data available from our previous experiments using aDBS and cDBS.Methods: We retrospectively analyzed data coming from 19 patients with PD undergoing surgery for STN-DBS electrode positioning and participating to experiments involving cDBS and aDBS delivery. Patients were all studied some days after the surgery (acute setting). The aTEED and dyskinesia assessments (Rush Dyskinesia Rating Scale, RDRS) considered in the Med ON-Stim ON condition.Results: We confirmed both that aTEED values and RDRS were significantly lower in the aDBS than in cDBS sessions (aTEED mean value, cDBS: 0.0278 ± 0.0011 j, vs. aDBS: 0.0071 ± 0.0003 j, p < 0.0001 Wilcoxon's rank sum; normalized RDRS mean score, cDBS: 0.66 ± 0.017 vs. aDBS: 0.45 ± 0.01, p = 0.025, Wilcoxon's rank sum test). In addition, we found a direct significant correlation between aTEED and RDRS (ρ = 0.44, p = 0.0032, Spearman's correlation).Conclusions: Our results provide a first piece of evidence that aTEED is correlated to the amount of levodopa-induced dyskinesias in patients with PD undergoing STN-DBS, thus supporting the role of aDBS as feasible and safe alternative to cDBS.

Striatal ΔFosB gene suppression inhibits the development of abnormal involuntary movements induced by L-Dopa in rats.

L-Dopa-induced dyskinesia (LID) is associated with upregulation of striatal ΔFosB in animal models and patients with Parkinson’s disease (PD). A mechanistic role of ΔFosB is suspected because its transgenic overexpression leads to early appearance of LID in rodents and primates. The present study in rodents is aimed at exploring the therapeutic potential of striatal ΔFosB gene suppression to control LID in patients with PD. To determine the effect of reducing striatal ΔFosB expression, we used RNAi gene knockdown in a rat model of PD and assessed abnormal involuntary movements (AIMs) in response to L-Dopa. Rats with dopamine depletion received striatal injections of rAAV-ΔFosB shRNA or a control virus before exposure to chronic L-Dopa treatment. Development of AIMs during the entire L-Dopa treatment period was markedly inhibited by ΔFosB gene knockdown and its associated molecular changes. The antiparkinsonian action of L-Dopa was unchanged by ΔFosB gene knockdown. These results suggest a major role for ΔFosB in the development of LID, and support exploring strategies to reduce striatal ΔFosB levels in patients with PD.

High levodopa plasma concentration after oral administration predicts levodopa-induced dyskinesia in Parkinson's disease

IntroductionIn patients with Parkinson's disease (PD), pulsatile dopaminergic stimulation may be a primary cause of levodopa-induced dyskinesia (LID). We aimed to investigate the correlation between levodopa pharmacokinetics (PK) and LID in PD. MethodsWe retrospectively reviewed the consecutive series of 255 PD patients without LID who underwent PK assessments with 100 mg levodopa. The type of peripheral decarboxylase inhibitor used in the PK assessments was determined by the usual prescription of the formulations of levodopa (10 mg carbidopa [n = 185] and 25 mg benserazide [n = 70]). ResultsDuring a median follow-up of 32 months (IQR, 16–49 months), 73 patients (29%) developed LID. Compared with patients who did not develop LID (PD–LID−), those who developed LID (PD–LID+) were younger (p = 0.003) and had significantly higher maximum levodopa concentration (Cmax) (p = 0.002) and area under the curve (p < 0.001), LEDD (p < 0.001), and improvement of motor symptoms (p = 0.009). In the multivariate Cox proportional hazards models, Cmax and AUC were associated with incident LID (Hazard Ratio [HR] 1.11, 95% confidence interval [CI] 1.03–1.19 and HR 1.13, 95% CI 1.03–1.24, respectively). In addition, younger age, benserazide use, LEDD, and MAOBI use were associated with incident LID. ConclusionHigh levodopa plasma concentration after oral administration was associated with incident LID in patients with PD.

White matter hyperintensities and risk of levodopa-induced dyskinesia in Parkinson's disease.

ObjectiveTo investigate whether the burden of white matter hyperintensities (WMHs) is associated with the risk of developing levodopa‐induced dyskinesia (LID) in Parkinson’s disease (PD).MethodsAccording to the Clinical Research Center for Dementia of South Korea WMH visual rating scale, 336 patients with drug‐naïve early stage PD (follow‐up >3 years) were divided into two groups of PD with minimal WMHs (PD‐WMH–; n = 227) and moderate‐to‐severe WMHs (PD‐WMH+; n = 109). The Cox regression model was used to estimate the hazard ratio for the development of LID in the PD‐WMH + group compared with the PD‐WMH– group, while adjusting for age at PD onset, sex, striatal dopamine depletion, and PD medication dose. Additionally, we assessed the effects of WMH burden rated by the Scheltens scale and regional WMH distribution on the development of LID.ResultsPatients in the PD‐WMH + group were older and had more severe parkinsonian motor signs despite comparable striatal dopamine transporter availability than those in the PD‐WMH– group. Patients in the PD‐WMH + group had a higher risk of developing LID (hazard ratio, 2.66; P < 0.001) than those in the PD‐WMH– group after adjustment for other confounding factors. A greater WMH burden was associated with earlier occurrence of LID (hazard ratio, 1.04; P = 0.001), although the effects of WMHs on LID development did not exhibit region‐specific patterns.InterpretationThe present study demonstrates that the burden of WMHs is associated with occurrence of LID in patients with PD, suggesting comorbid WMHs as a risk factor for LID.

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Safety and Efficacy of Levetiracetam for the Management of Levodopa- Induced Dyskinesia in Patients with Parkinson's Disease: A Systematic Review.

Levetiracetam, a novel antiepileptic drug, has shown antidyskinetic effects in experimental animal models of Parkinson's disease (PD). The tolerability and efficacy of levetiracetam in reducing the levodopa-induced dyskinesia (LID) in PD patients have not been established. Therefore, this study aims to synthesize evidence from published prospective clinical trials about the efficacy of levetiracetam for the management of LID in PD patients. We followed the PRISMA statement guidelines during the preparation of this systematic review. A computer literature search of PubMed, EBSCO, Scopus, MEDLINE, and the web of science was carried out. We selected prospective clinical trials assessing the anti-dyskinetic efficacy of levetiracetam for treating LID in patients with PD. The Abnormal Involuntary Movement Scale (AIMS), Clinical Global Impression Score (GCI), UPDRS III, and UPDRS IV were considered as the primary outcome measures; their data were extracted and reviewed. Our review included seven clinical trials with a total of 150 patients. Of them, three studies were randomized controlled trials, and the remaining were open-label single arm trials. Four studies reported poor tolerability of the levetiracetam with mild anti-dyskinetic effects. Levetiracetam slightly improved the UPDRS-IV and AIMS scores with small effect size. In the remaining three studies, levetiracetam failed to exhibit any anti-dyskinetic effects. Current evidence does not support the efficacy of the levetiracetam for treating LID in PD patients, however, due to the limited number of published randomized control trials (RCTs), further RCTs are required.

A Study to Assess the Safety and Effectiveness of Pridopidine Compared to Placebo in the Treatment of Levodopa-Induced Dyskinesia in Patients With Parkinson's Disease

A Study to Assess the Safety and Effectiveness of Pridopidine Compared to Placebo in the Treatment of Levodopa-Induced Dyskinesia in Patients With Parkinson's Disease

Early Dyskinesias in Parkinson's Disease Patients With Parkin Mutation: A Primary Corticostriatal Synaptopathy?

Mutations in the PARKIN gene cause early-onset Parkinson’s disease (PD). Despite the high proportion of still missing phenotyping data in the literature devoted to early-onset PD, studies suggest that, as compared with late-onset PD, PARKIN patients show dystonia at onset and extremely dose-sensitive levodopa-induced dyskinesia (LID). What pathophysiological mechanisms underpin such early and atypical dyskinesia in patients with PARKIN mutations? Though the precise mechanisms underlying dystonia and LID are still unclear, evidence suggests that hyperkinetic disorders in PD are a behavioral expression of maladaptive functional and morphological changes at corticostriatal synapses induced by long-term dopamine (DA) depletion. However, since the dyskinesia in PARKIN patients can also be present at onset, other mechanisms beside the well-established DA depletion may play a role in the development of dyskinesia in these patients. Because cortical and striatal neurons express parkin protein, and parkin modulates the function of ionotropic glutamatergic receptors (iGluRs), an intriguing explanation may rest on the potential role of parkin in directly controlling the glutamatergic corticostriatal synapse transmission. We discuss the novel theory that loss of parkin function can dysregulate transmission at the corticostriatal synapses where they cause early maladaptive changes that co-occur with the changes stemming from DA loss. This hypothesis suggests an early striatal synaptopathy; it could lay the groundwork for pharmacological treatment of dyskinesias and LID in patients with PARKIN mutations.

Polymorphisms of Catechol-O-Methyl Transferase (COMT) Gene in Vulnerability to Levodopa-Induced Dyskinesia

Parkinson's disease (PD), a common neurodegenerative disorder, is usually treated with Levodopa (L-DOPA). The use of this drug, however, is severely limited by the development of side effects of the motor system: Levodopa-induced dyskinesia (LID). The aim of this study is to investigate the association between seven COMT gene single-nucleotide polymorphisms (SNPs) and the development of LID in patients with PD. 232 Caucasian patients with PD were investigated. 212 patients with PD received Levodopatherapy. Dyskinesia was assessed with the use of the Abnormal Involuntary Movement Scale (AIMS). Genotyping was carried out on seven SNPs of the COMT gene (rs4680, rs6269, rs4633, rs4818, rs769224, rs165774, rs174696) using a real-time PCR method, and blind to the clinical status of the subjects. We found association between four SNPs, rs165774, rs4818, rs4633, rs4680, and LID. When the duration of disease was added as a covariate in regression analysis, however, the results did not reach statistical significance. Only the additive model for rs165774 was found to be close to be statistical significance (OR = 1.627 [0.976-2.741], permutation p = 0.057). The results failed to clearly support a contribution of the studied polymorphisms; this may be related to a dominant relationship with the disease duration confounding the effect on the prevalence of LID.

Amantadine extended-release capsules for levodopa-induced dyskinesia in patients with Parkinson's disease.

Levodopa-induced dyskinesia (LID) is a common motor complication in patients with Parkinson’s disease on chronic levodopa therapy. The management of LID is important as dyskinesia can be disabling and impair quality of life. Currently, there are limited treatment options for the medical management of LID. Amantadine extended-release capsules (Gocovri™) is the first medication that received US Food and Drug Administration approval for the treatment of LID. The following is a review of the pharmacodynamics, efficacy and safety profile, and current state of treatment of amantadine for LID.

The association between early treatment with amantadine and delayed onset of levodopa-induced dyskinesia in patients with Parkinson’s disease

The association between early treatment with amantadine and delayed onset of levodopa-induced dyskinesia in patients with Parkinson’s disease

Presynaptic dopamine depletion determines the timing of levodopa-induced dyskinesia onset in Parkinson's disease.

Reduced presynaptic dopaminergic activity plays an important role in the development of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD). In this study, we investigated whether dopaminergic function in the nigrostriatal system is associated with the timing of LID onset. From among 412 drug-naive PD patients who underwent a dopamine transporter (DAT) PET scan during their baseline evaluation, we enrolled 65 patients who developed LID during a follow-up period of >2years. Based on the time from PD onset, LID was classified as early, intermediate or late onset. We then compared DAT availability in the striatal subregions of the patients in the three groups. The demographic characteristics did not differ among the three patient groups except for earlier intervention of levodopa therapy in the early LID onset group (p=0.001). After adjusting for age at PD onset, gender, timing of levodopa therapy from PD onset, and the severity of PD motor symptoms, DAT activity in the posterior putamen was found to be significantly lower in the early LID onset group than in the late LID onset group (p=0.017). Multivariate linear regression analysis showed that low DAT activity in the posterior putamen was significantly associated with the early appearance of LID in the early LID onset group (β=16.039, p=0.033). This study demonstrated that low DAT activity in the posterior putamen at baseline is a major risk factor for the early onset of LID in patients with PD, suggesting that the degree of presynaptic dopaminergic denervation plays an important role in determining the timing of LID onset.

P.5.d.009 - Predictive genetic model for levodopa-induced dyskinesia in patients with Parkinson’s disease

Predictive genetic model for levodopa-induced dyskinesia in patients with Parkinson's disease S.A. Ivanova(1), V.M. Alifirova(2), M.B. Freidin(3), I.V. Pozhidaev(4), O.Y. Fedorenko(4), N.A. Bokhan(4), I.A. Zhukova(5), N.G. Zhukova(5), B. Wilffert(6), A.J.M. Loonen(6) (1)Mental Health Research Institute, Molecular Genetics and Biochemistry Laboratory, Tomsk, Russia (2)Siberian State Medical University, Department of Neurology and Neurosurgery, Tomk, Russia (3)Tomsk National Research Medical Center of the Russian Academy of Sciences, Research Institute of Medical Genetics, Tomsk, Russia (4)Tomsk National Research Medical Center of the Russian Academy of Sciences, Mental Health Research Institute, Tomsk, Russia (5)Siberian State Medical University, Department of Neurology and Neurosurgery, Tomsk, Russia (6)University of Groningen, Groningen Research Institute of Pharmacy, Groningen, The Netherlands Parkinson's disease (PD), a common neurodegenerative disorder caused by the loss of the dopaminergic input to the basal ganglia, is commonly treated with levodopa (L-DOPA). The use of this drug, however, is severely limited by adverse effects. Levodopa-induced dyskinesia (LID) is one of these and characterized by involuntary muscle movements that occur as a consequence of chronic levodopa treatment. LID is a substantial barrier to effective symptomatic management of PD as up to 45% of L-DOPA users develop LID within 5 years [1]. Clinical heterogeneity of LID suggests a significant role of endogenous factors in determining their prevalence. Some evidences suggest a relationship between LID and specific genetic variants, such as polymorphisms in the genes controlling enzymes responsible for drug and monoamine metabolism, neurotransmitter receptors and proteins involved in oxidative stress or antioxidant function [2–4]. Objective: To investigate a contribution of polymorphic variants of neurotransmitter receptors and cytochrome genes in the development of LID in PD patients. Methods: A total of 212 PD patients who received L-DOPA therapy were studied. Dyskinesia was assessed by using the Abnormal Involuntary Movement Scale (AIMS). DNA extraction and genotyping were conducted according to standard protocols and blind to the clinical status of the subjects. Genotyping was carried out for 72 SNPs of DRD1, DRD2, DRD2/ANKK1, DRD3, DRD4, HTR2C, HTR3A, HTR3B, HTR6, HTR2A, HTR1A, HTR1B, CYP1A2*1F, CYP2D6*3, CYP2D6*4, CYP2C19*3, CYP2C19*17, CYP2C19*2, and GSTP1 genes using MassARRAY® Analyzer 4 (Agena Bioscience™) and the set SEQUENOM Consumables iPLEX Gold 384. Discriminant analysis and receiver operating curve (ROC)-analysis were carried out to build a genetic predictive model for dyskinesia. Results: Group of PD patients consists of 149 females and 83 males (age ranging from 40 to 86 years, average age 68.7 ± 7.6 years). The mean age of onset is 60.04 ± 9.46 years, average disease duration is 9.79 ± 5.57 years. Dyskinesia was reported in 57 (26.9%) patients. The best discriminant model was obtained with the following predictors: rs11721264, rs165774, rs3758653, rs4245147, rs6313, rs1364043, rs2734849, rs324035, rs6311, rs11246226 and rs4244285. These polymorphisms are localized in the following genes: DRD3 (rs11721264, rs324035), DRD4 (rs3758653, rs11246226), DRD2 (rs4245147, rs2734849), HTR2A (rs6313, rs6311), HTR1A (rs1364043). The discriminant model using this set of SNPs gives the error of classification about 13% and the AUC 0.795. Depending on the anticipated frequency of LID, positive and negative predictor values varied between 0.745–0.834 and 0.864–0.916, respectively. We hypothesized in our previous studies that the pathological basis of LID might be degeneration of indirect pathway medium spiny neurons [5]. These indirect pathway medium spiny neurons carry type 2 family dopamine receptors (DRD2, DRD3, DRD4), and HTR2A receptors. Moreover, dopamine release may be promoted by inhibiting serotonergic neurotransmission. Hence, the current findings are well in line with this hypothesis. Conclusion: The resulting panel of 11 SNPs provides a sufficiently high accuracy of LID prediction. The use of this panel in a prospective study will clarify the prospects for its application in clinical practice for predicting risk of LID in patients with PD.