Idazoxan, an alpha-2 antagonist, and L-DOPA-induced dyskinesias in patients with Parkinson's disease

Mov Disord. 2001 Jul;16(4):708-13. doi: 10.1002/mds.1143.

Abstract

Dyskinesia is a frequent and disabling side effect in patients with Parkinson's disease treated with chronic dopa-therapy. Preclinical data in the 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) monkey suggest that alpha-2 antagonists may reduce dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. We assessed, in a pilot randomised placebo-controlled study, the effects of single oral doses (10 mg, 20 mg, and 40 mg) of idazoxan, an alpha-2 antagonist, on motor parkinsonian disability and L-DOPA-induced dyskinesia following an acute oral challenge of L-DOPA in 18 patients with Parkinson's disease. The severity of L-DOPA-induced dyskinesia improved after 20 mg idazoxan pretreatment, while there was no concommittant deterioration in the antiparkinsonian response to L-DOPA. These results suggest that blocking alpha-2 receptors in patients with Parkinson's disease might improve L-DOPA-induced dyskinesia without the cost of a return of parkinsonian symptomatology. Further studies are required to assess whether this property could have potential therapeutic applications in the long-term management of dyskinetic patients with Parkinson's disease.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adrenergic alpha-Antagonists / adverse effects
  • Adrenergic alpha-Antagonists / therapeutic use*
  • Aged
  • Antiparkinson Agents / adverse effects*
  • Antiparkinson Agents / therapeutic use
  • Dose-Response Relationship, Drug
  • Dyskinesia, Drug-Induced / drug therapy*
  • Female
  • Humans
  • Idazoxan / adverse effects
  • Idazoxan / therapeutic use*
  • Levodopa / adverse effects*
  • Levodopa / therapeutic use
  • Male
  • Middle Aged
  • Neurologic Examination / drug effects
  • Parkinson Disease / drug therapy*
  • Pilot Projects

Substances

  • Adrenergic alpha-Antagonists
  • Antiparkinson Agents
  • Levodopa
  • Idazoxan