Idazoxan, an alpha-2 antagonist, and L-DOPA-induced dyskinesias in patients with Parkinson's disease.
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.
Rascol
O
O
Department of Clinical Pharmacology, Clinical Investigation Centre and INSERM U455, University Hospital, Toulouse, France. rascol@cict.fr
Arnulf
I
I
Peyro-Saint Paul
H
H
Brefel-Courbon
C
C
Vidailhet
M
M
Thalamas
C
C
Bonnet
A M
AM
Descombes
S
S
Bejjani
B
B
Fabre
N
N
Montastruc
J L
JL
Agid
Y
Y
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
D000317:Adrenergic alpha-Antagonists; D000978:Antiparkinson Agents; D007980:Levodopa; D019329:Idazoxan