title: Idazoxan, an alpha-2 antagonist, and L-DOPA-induced dyskinesias in patients with Parkinson's disease.
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.
authors.affiliation: Department of Clinical Pharmacology, Clinical Investigation Centre and INSERM U455, University Hospital, Toulouse, France. rascol@cict.fr
authors.forename: O
authors.initials: O
authors.lastname: Rascol
authors.forename: I
authors.initials: I
authors.lastname: Arnulf
authors.forename: H
authors.initials: H
authors.lastname: Peyro-Saint Paul
authors.forename: C
authors.initials: C
authors.lastname: Brefel-Courbon
authors.forename: M
authors.initials: M
authors.lastname: Vidailhet
authors.forename: C
authors.initials: C
authors.lastname: Thalamas
authors.forename: A M
authors.initials: AM
authors.lastname: Bonnet
authors.forename: S
authors.initials: S
authors.lastname: Descombes
authors.forename: B
authors.initials: B
authors.lastname: Bejjani
authors.forename: N
authors.initials: N
authors.lastname: Fabre
authors.forename: J L
authors.initials: JL
authors.lastname: Montastruc
authors.forename: Y
authors.initials: Y
authors.lastname: Agid
mesh_terms: D000284:Administration, Oral; D000317:Adrenergic alpha-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D005260:Female; D006801:Humans; D019329:Idazoxan / Q000009:adverse effects / Q000627:therapeutic use*; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy*; D010865:Pilot Projects
chemical_list: D000317:Adrenergic alpha-Antagonists; D000978:Antiparkinson Agents; D007980:Levodopa; D019329:Idazoxan