Mu- and delta-opioid receptor antagonists reduce levodopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson's disease.
Long-term treatment of Parkinson's disease with levodopa is complicated by the emergence of involuntary movements, known as levodopa-induced dyskinesia. It has been hypothesized that increased opioid transmission in striatal output pathways may be responsible for the generation of dyskinesia. In this study, we have investigated the effect of blockade of opioid peptide transmission on levodopa-induced dyskinesia in a primate model of Parkinson's disease-the MPTP-lesioned marmoset. Coadministration of nonselective and mu- or delta-subtype-selective opioid receptor antagonists with levodopa resulted in a significant decrease in dyskinesia. There was no attenuation of the anti-parkinsonian actions of levodopa. These data suggest that specific mu- or delta-opioid receptor antagonists might be applicable clinically in the treatment of levodopa-induced dyskinesia in Parkinson's disease.
Henry
B
B
Manchester Movement Disorder Laboratory, 1.124 Division of Neuroscience, School of Biological Sciences, University of Manchester, Stopford Building, Manchester, M13 9PT, United Kingdom.
Fox
S H
SH
Crossman
A R
AR
Brotchie
J M
JM
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002144:Callithrix; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D020820:Dyskinesias / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D005260:Female; D018476:Hypokinesia / Q000139:chemically induced / Q000188:drug therapy; D007980:Levodopa / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D009019:Morphinans / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D011187:Posture; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*
D009019:Morphinans; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C058450:cyprodime; C051844:norbinaltorphimine; D007980:Levodopa; D009271:Naltrexone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C055382:naltrindole