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.