The effects of cysteamine in a mouse model of levodopa-induced dyskinesias

Neurosci Lett. 2018 Jan 1:662:395-401. doi: 10.1016/j.neulet.2017.10.062. Epub 2017 Oct 31.

Abstract

Levo-dopa (L-DOPA) has shown significant and long-lasting efficacy in the treatment of motor features characteristic of Parkinson's disease (PD). However, the effects tend to wear off at a time typically when side-effects, such as L-DOPA induced dyskinesias (LIDs), start to emerge and for which the treatment options are very limited. In recent years, we have reported on the neuroprotective and neurorestorative properties of the compounds cystamine/cysteamine in ameliorating several aspects of PD. Building on these observations, we set out to further evaluate the benefits of cysteamine on LIDs. We thus treated mice displaying LIDs with single cysteamine challenges at various doses (20, 50 and 30mg/kg) or chronically for 2 weeks using cysteamine at a dose of 30mg/kg. None of the regimens nor doses ameliorated any LID-related behavioral impairments. Mice displaying LIDs did, however, respond to a single treatment of 60mg/kg of amantadine, a drug used to clinically manage LIDs. Taken together, our results suggest that cysteamine does not induce benefits on LIDs, at least at the doses and regimen tested in our study. However, the disease-modifying effects depicted by cystamine/cysteamine, which we have shown in several reports, would strongly encourage its continued evaluation in the clinical setting.

Keywords: Amantadine; Axial; Cystamine; Limb dyskinesias; Orolingual; Parkinson’s disease.

MeSH terms

  • Animals
  • Cysteamine / pharmacology*
  • Cystine Depleting Agents / pharmacology*
  • Disease Models, Animal
  • Dopamine Agents / toxicity
  • Dyskinesia, Drug-Induced / drug therapy*
  • Levodopa / toxicity
  • Mice

Substances

  • Cystine Depleting Agents
  • Dopamine Agents
  • Levodopa
  • Cysteamine