Non-subtype-selective opioid receptor antagonism in treatment of levodopa-induced motor complications in Parkinson's disease.
Opioid peptide transmission is enhanced in the striatum of animal models and Parkinson's disease (PD) patients with levodopa-induced motor complications. Opioid receptor antagonists reduce levodopa-induced dyskinesia in primate models of PD; however, clinical trials to date have been inconclusive. A double-blind, placebo controlled, crossover design study in 14 patients with PD experiencing motor fluctuations was carried out, using the non-subtype-selective opioid receptor antagonist naloxone. Naloxone did not reduce levodopa-induced dyskinesia. The duration of action of levodopa was increased significantly by 17.5%. Non-subtype-selective opioid receptor antagonism may prove useful in the treatment of levodopa-related wearing-off in PD but not in dyskinesia.
Fox
Susan
S
The Walton Centre for Neurology and Neurosurgery, Liverpool, United Kingdom. sfox@uhnres.utoronto.ca
Silverdale
Montague
M
Kellett
Mark
M
Davies
Rhys
R
Steiger
Malcolm
M
Fletcher
Nicholas
N
Crossman
Alan
A
Brotchie
Jonathan
J
D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000627:therapeutic use; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000209:etiology*; D005500:Follow-Up Studies; D006801:Humans; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D009270:Naloxone / Q000008:administration & dosage / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy*; D014743:Videotape Recording
D000978:Antiparkinson Agents; D009292:Narcotic Antagonists; D009270:Naloxone; D007980:Levodopa