Long‐term antidyskinetic efficacy of amantadine in Parkinson's disease

Wolf, Elisabeth; Seppi, Klaus; Katzenschlager, Regina; Hochschorner, Guenter; Ransmayr, Gerhard; Schwingenschuh, Petra; Ott, Erwin; Kloiber, Iris; Haubenberger, Dietrich; Auff, Eduard; Poewe, Werner

doi:10.1002/mds.23034

Cited by 172 publications

(103 citation statements)

References 27 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…More recently, amantadine was reported to improve levodopa‐induced dyskinesia (LID) 4, 5, 6, 7. The clinical use of amantadine is limited because of tolerability issues, although doses up to a maximum of 400 mg/d, in divided doses, are approved for use in PD.…”

mentioning

confidence: 99%

Amantadine extended release for levodopa‐induced dyskinesia in Parkinson's disease (EASED Study)

et al. 2015

View full text Add to dashboard Cite

ADS‐5102 is a long‐acting, extended‐release capsule formulation of amantadine HCl administered once daily at bedtime. This study investigated the safety, efficacy, and tolerability of ADS‐5102 in Parkinson's disease (PD) patients with levodopa‐induced dyskinesia. This was a randomized, double‐blind, placebo‐controlled, parallel‐group study of 83 PD patients with troublesome dyskinesia assigned to placebo or one of three doses of ADS‐5102 (260 mg, 340 mg, 420 mg) administered daily at bedtime for 8 weeks. The primary efficacy analysis compared change from baseline to week 8 in Unified Dyskinesia Rating Scale (UDysRS) total score for 340 mg ADS‐5102 versus placebo. Secondary outcome measures included change in UDysRS for 260 mg, 420 mg, Fatigue Severity Scale (FSS), Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS), patient diary, Clinician's Global Impression of Change, and Parkinson's Disease Questionnaire (PDQ‐39). ADS‐5102 340 mg significantly reduced dyskinesia versus placebo (27% reduction in UDysRS, P = 0.005). In addition, ADS‐5102 significantly increased ON time without troublesome dyskinesia, as assessed by PD patient diaries, at 260 mg (P = 0.004), 340 mg (P = 0.008) and 420 mg (P = 0.018). Adverse events (AEs) were reported for 82%, 80%, 95%, and 90% of patients in the placebo, 260‐mg, 340‐mg, and 420‐mg groups, respectively. Constipation, hallucinations, dizziness, and dry mouth were the most frequent AEs. Study withdrawal rates were 9%, 15%, 14%, and 40% for the placebo, 260‐mg, 340‐mg, and 420‐mg groups, respectively. All study withdrawals in the active treatment groups were attributable to AEs. ADS‐5102 was generally well tolerated and resulted in significant and dose‐dependent improvements in dyskinesia in PD patients. © 2015 Adamas Pharmaceuticals, Inc. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

show abstract

mentioning

confidence: 99%

Amantadine extended release for levodopa‐induced dyskinesia in Parkinson's disease (EASED Study)

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Administration of the NMDA noncompetitive antagonist amantadine to MPTP-treated monkeys 7,8,21 or to PD patients 42,84 has been shown to reduce LID. It has been proposed that the NR2B subunit is involved in the development of LID because its binding sites increase both in dyskinetic patients and in MPTP-treated monkeys.…”

Section: Nmda Nr1/nr2b Receptor Bindingmentioning

confidence: 99%

Changes in glutamate receptors in dyskinetic parkinsonian monkeys after unilateral subthalamotomy

Jourdain

Morin

Grégoire

et al. 2015

JNS

View full text Add to dashboard Cite

abbreviatioNs AMPA = α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; GP = globus pallidus; GPe = GP externus; GPi = GP internus; LID = levodopa-induced dyskinesia; mGlu = metabotropic glutamate; MPTP = 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NMDA = N-methyl-d-aspartate; PD = Parkinson disease; STN = subthalamic nucleus; 6-OHDA = 6-hydroxydopamine. obJect Unilateral subthalamotomy is a surgical procedure that may be used to alleviate disabling levodopa-induced dyskinesias (LIDs) in patients with Parkinson disease (PD). However, the mechanisms involved in LID remain largely unknown. The subthalamic nucleus (STN) is the sole glutamatergic nucleus within the basal ganglia, and its lesion may produce changes in glutamate receptors in various areas of the basal ganglia. The authors aimed to investigate the biochemical changes in glutamate receptors in striatal and pallidal regions of the basal ganglia after lesion of the STN in parkinsonian macaque monkeys. methods The authors treated 12 female ovariectomized monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD-like symptoms, treated 8 of these animals with 3,4-dihydroxy-l-phenylalanine (L-DOPA; levodopa) to induce LID, and performed unilateral subthalamotomy in 4 of these 8 monkeys. Four additional monkeys were treated with saline only and were used as controls. The MPTP monkeys had previously been shown to respond behaviorally to lower doses of levodopa after the STN lesion. Autoradiography of slices from postmortem brain tissues was used to visualize changes in the specific binding of striatal and pallidal ionotropic glutamate receptors (that is, of the α-amino-3-hydroxy 5-methyl-4-isoxazole propionate [AMPA] and N-methyl-d-aspartate [NMDA] NR1/NR2B subunit receptors) and of metabotropic glutamate (mGlu) receptors (that is, mGlu2/3 and mGlu5 receptors). The specific binding and distribution of glutamate receptors in the basal ganglia of the levodopa-treated, STN-lesioned MPTP monkeys were compared with those in the saline-treated control monkeys and in the saline-treated and levodopa-treated MPTP monkeys. results The autoradiographic results indicated that none of the pharmacological and surgical treatments produced changes in the specific binding of AMPA receptors in the basal ganglia. Levodopa treatment increased the specific binding of NMDA receptors in the basal ganglia. Subthalamotomy reversed these increases in the striatum, but in the globus pallidus (GP), the subthalamotomy reversed these increases only contralaterally. Levodopa treatment reversed MPTPinduced increases in mGlu2/3 receptors only in the GP. mGlu2/3 receptor-specific binding in the striatum and GP decreased bilaterally in the levodopa-treated, STN-lesioned MPTP monkeys compared with the other 3 groups. Compared with mGlu5 receptor-specific binding in the control monkeys, that of the levodopa-treated MPTP monkeys increased in the dorsal putamen and remained unchanged in the caudate nucleus and in the GP. coNclusioNs These results implicate glutamate recepto...

show abstract

“…Aside from titrating the dose of levodopa to try to avoid its occurrence, glutamatergic antagonists provide an additional approach. The only available agent of this type currently that exhibits an anti-dyskinetic effect is amantadine, [8][9][10] although it may be associated with a number of adverse effects, and new strategies for controlling dyskinesia are needed.…”

Section: Current Treatment Challenges and Unmet Needs In Mid-to Late-mentioning

confidence: 99%

Progression of Parkinson’s Disease and Unmet Needs in Mid- to Late-stage Patients

Reichmann¹,

Barone²,

Poewe³

2015

European Neurological Review

Self Cite

View full text Add to dashboard Cite

In early-stage Parkinson's disease (PD), dopaminergic treatment is highly effective in controlling motor symptoms. However, as the disease progresses, other symptoms and comorbidities need to be addressed, such as suboptimal motor control, emerging motor complications (e.g. nocturnal and early-morning akinesia/tremor, early wearing-off and dyskinesia), emerging levodopa-resistant motor symptoms, increasing non-motor symptoms and treatment of non-dopaminergic symptoms. Despite these unmet needs, no new therapies for PD have been introduced into routine clinical practice over the past 10 years. Safinamide is a new oral therapy that has both dopaminergic and non-dopaminergic mechanisms of action. In phase III clinical trials, safinamide has demonstrated significant clinical benefits in patients with mid-to late-stage PD experiencing motor fluctuations as an add-on therapy to levodopa and other PD medication versus those treated only on an optimised PD therapy. This includes improvements in daily ON time, improvements in motor function and beneficial effects on dyskinesia that have been studied in patients for up to 2 years. Safinamide is well tolerated, and it is a new and unique agent in the armamentarium of treatments for patients with mid-to late-stage PD experiencing motor fluctuations.

show abstract

Long‐term antidyskinetic efficacy of amantadine in Parkinson's disease

Cited by 172 publications

References 27 publications

Amantadine extended release for levodopa‐induced dyskinesia in Parkinson's disease (EASED Study)

Amantadine extended release for levodopa‐induced dyskinesia in Parkinson's disease (EASED Study)

Changes in glutamate receptors in dyskinetic parkinsonian monkeys after unilateral subthalamotomy

Progression of Parkinson’s Disease and Unmet Needs in Mid- to Late-stage Patients

Contact Info

Product

Resources

About