Pridopidine, a clinic‐ready compound, reduces 3,4‐dihydroxyphenylalanine‐induced dyskinesia in Parkinsonian macaques

  title={Pridopidine, a clinic‐ready compound, reduces 3,4‐dihydroxyphenylalanine‐induced dyskinesia in Parkinsonian macaques},
  author={Tom H. Johnston and Michael Geva and Lilach Steiner and Aric Orbach and Spyros Papapetropoulos and Juha Matti Savola and Ian J Reynolds and Paul D. Ravenscroft and Michael P. Hill and Susan H. Fox and Jonathan M. Brotchie and Ralph Laufer and Michael R. Hayden},
  journal={Movement Disorders},
Pridopidine, in development for Huntington's disease, may modulate aberrant l‐dopa‐induced effects including l‐dopa‐induced dyskinesia (LID). 
Receptor Ligands as Helping Hands to L-DOPA in the Treatment of Parkinson’s Disease
Recent investigations about non-dopaminergic central nervous system (CNS) receptor ligands that have been identified to have therapeutic potential for the treatment of motor and non-motor symptoms of Parkinson’s disease are focused on.
Pathophysiological Mechanisms and Experimental Pharmacotherapy for L-Dopa-Induced Dyskinesia
This review provides an updated report of experimental pharmacotherapies tested in clinical trials of PD patients and drugs currently under study to alleviate LID, and describes the known pathophysiological mechanisms of LID.
Pridopidine reduces mutant huntingtin‐induced endoplasmic reticulum stress by modulation of the Sigma‐1 receptor
It is shown that pridopidine significantly ameliorates mHtt‐induced ER stress in cellular HD models, starting at low nanomolar concentrations, and increases toxic oligomeric mHTT recruitment into less toxic large sodium dodecyl sulfate‐insoluble aggregates, suggesting that this in turn reduces ER stress and cytotoxicity.
Using sigma-ligands as part of a multi-receptor approach to target diseases of the brain
The potential role of the sigma receptors and their ligands as part of a multi receptor approach in the treatment of degenerative diseases of the CNS and the development of multi-drug combinations to target multiple receptors is discussed.
Bi-phasic dose response in the preclinical and clinical developments of sigma-1 receptor ligands for the treatment of neurodegenerative disorders
  • T. Maurice
  • Biology
    Expert opinion on drug discovery
  • 2020
The data showing the high therapeutic potential of S1R drugs for the treatment of neurodegenerative diseases are presented, focusing on pridopidine as a potent and selective S 1R agonist under clinical development.
Pridopidine modifies disease phenotype in a SOD1 mouse model of amyotrophic lateral sclerosis
Results show that pridopidine can modify the disease phenotype of ALS‐associated cachexia and motor deficits in a SOD1 G93A mouse model of ALS.
Cholinergic Receptor Modulation as a Target for Preventing Dementia in Parkinson’s Disease
The cholinergic system is discussed as a therapeutic target of cotinine to prevent cognitive symptoms and transition to dementia in PD.
Non-Dopaminergic Treatments for Motor Control in Parkinson’s Disease: An Update
Drug repurposing continues to be a key strategy for non-dopaminergic targets in PD, but the field needs to increase discovery and availability of such drugs.


The Pharmacology of l-DOPA-Induced Dyskinesia in Parkinson’s Disease
It is proposed that to optimally alleviate this motor complication of Parkinson’s disease, it may be necessary to develop combined treatment approaches that will target simultaneously more than one neurotransmitter system.
TC-8831, a nicotinic acetylcholine receptor agonist, reduces l-DOPA-induced dyskinesia in the MPTP macaque
Amantadine reduces levodopa‐induced dyskinesias in parkinsonian monkeys
Results lend support to the view that glutamate receptormediated mechanisms contribute to levodopa‐induced dyskinesias and suggest that amantadine could alleviate such complications in parkinsonian patients, especially with careful dose optimization.
Stimulation of cannabinoid receptors reduces levodopa‐induced dyskinesia in the MPTP‐lesioned nonhuman primate model of Parkinson's disease
Testing the hypothesis that the cannabinoid receptor agonist nabilone would alleviate levodopa‐induced dyskinesia in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine hydrochloride ‐lesioned marmoset model of Parkinson's disease found it to be useful in the treatment of motor complications in Parkinson’s disease.
Fipamezole (JP‐1730) is a potent α2 adrenergic receptor antagonist that reduces levodopa‐induced dyskinesia in the MPTP‐lesioned primate model of Parkinson's disease
  • J. Savola, M. Hill, J. Brotchie
  • Biology, Psychology
    Movement disorders : official journal of the Movement Disorder Society
  • 2003
A novel α2 antagonist, fipamezole (JP‐1730), which has high affinity at human α2A, α2B, and α2C receptors and potential as an anti‐dyskinetic agent in the treatment of Parkinson's disease is described.
Attenuation of levodopa-induced dyskinesia by normalizing dopamine D3 receptor function
Results indicated that the D3 receptors participated in both dyskinesia and the therapeutic action of levodopa, and that partial agonists may normalize D3 receptor function and correct side effects of levidopa therapy in patients with Parkinson disease.
In vivo pharmacology of the dopaminergic stabilizer pridopidine.
Randomized clinical trial of fipamezole for dyskinesia in Parkinson disease (FJORD study)
The evidence of efficacy in the US subgroup suggested that fipamezole at 90 mg TID may be useful to treat LID in PD without exacerbating parkinsonism.