The alpha2-adrenergic receptor antagonist idazoxan reduces dyskinesia and enhances anti-parkinsonian actions of L-dopa in the MPTP-lesioned primate model of Parkinson's disease

Mov Disord. 1999 Sep;14(5):744-53. doi: 10.1002/1531-8257(199909)14:5<744::aid-mds1006>;2-7.


Dopamine replacement therapy in patients with Parkinson's disease is plagued by the emergence of abnormal involuntary movements known as L-dopa-induced dyskinesias. It has been demonstrated that yohimbine can reduce L-dopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson's disease. Yohimbine is, among other things, an alpha-adrenergic receptor antagonist. In this study, we demonstrate that the selective and potent alpha2-adrenergic receptor antagonist idazoxan reduces L-dopa-induced dyskinesia in the MPTP-lesioned marmoset model of Parkinson's disease. The alpha2-adrenergic receptor antagonists rauwolscine and yohimbine also reduce L-dopa-induced dyskinesia. Furthermore, we demonstrate that coadministration of idazoxan with L-dopa can provide an anti-parkinsonian action more than twice the length of that seen with L-dopa alone. However, idazoxan as a monotherapy displayed no anti-parkinsonian actions. We propose that idazoxan in combination with L-dopa may provide a novel approach to the treatment of Parkinson's disease that will not only reduce the dyskinetic side effects, but extend the anti-parkinsonian actions of L-dopa. Idazoxan, as an adjunct to dopamine replacement, may prove useful in the treatment of parkinsonian patients at all stages of disease progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacokinetics*
  • Adrenergic Antagonists / pharmacology*
  • Adrenergic Antagonists / therapeutic use*
  • Animals
  • Antiparkinson Agents / metabolism*
  • Brain / metabolism*
  • Callithrix
  • Disease Models, Animal*
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Dyskinesias / drug therapy*
  • Female
  • Idazoxan / pharmacology*
  • Idazoxan / therapeutic use*
  • Levodopa / metabolism*
  • Male
  • Receptors, Adrenergic, alpha-2 / drug effects*
  • Time Factors
  • Yohimbine / pharmacology
  • Yohimbine / therapeutic use


  • Adrenergic Antagonists
  • Antiparkinson Agents
  • Receptors, Adrenergic, alpha-2
  • Yohimbine
  • Levodopa
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Idazoxan