Search for "(sinemet and side-effects)" in Medscape's
free Full-Text Articles or
the Medscape Bookstore
Title
Glial cell line-derived neurotrophic factor-levodopa interactions
and reduction of side effects in parkinsonian monkeys.
Author
Miyoshi Y; Zhang Z; Ovadia A; Lapchak PA; Collins F; Hilt D; Lebel
C; Kryscio R; Gash DM
Address
Department of Anatomy and Neurobiology, University of Kentucky,
College of Medicine, Lexington, USA.
Source
Ann Neurol, 42(2):208-14 1997 Aug
Abstract
Glial cell line-derived neurotrophic factor (GDNF) stimulates the
nigrostriatal dopaminergic pathway and improves motor
functions in animal models of parkinsonism. Sinemet is currently
the most widely used drug for treating Parkinson's
disease. The present study has evaluated GDNF-Sinemet interactions
in parkinsonian rhesus monkeys. Both GDNF
and Sinemet, when given alone, significantly improved total
parkinsonian scores. The response to Sinemet did not
change after intracerebroventricular vehicle injections. In
contrast, there was a functional interaction between GDNF and
levodopa. When comparing the levodopa dose response before and
after GDNF treatment, significant behavioral
improvements were seen after trophic factor administration at every
levodopa dose level except 500 mg. Adverse
responses to Sinemet treatment alone in parkinsonian animals
included vomiting, dykinesias, dystonias, and stereotypic
movements. Combined GDNF-Sinemet treatment significantly reduced
the occurrence of these levodopa-induced side
effects, with a >90% decrease in adverse responses seen at the
mid-Sinemet (250 mg levodopa-25 mg carbidopa)
dose level. The only side effect from GDNF treatment was a
transitory weight loss. Thus, combined GDNF-Sinemet
treatment could be of therapeutic value in treating parkinsonism,
by producing a greater functional response and by
mitigating adverse responses to Sinemet treatment.
Language
Eng
Unique Identifier
97410016
MESH Headings
Animal; Antiparkinson Agents (PD/*TO/TU); Carbidopa (PD/*TO/TU);
Cerebral Ventricles (DE/PH/PP);
Dose-Response Relationship, Drug; Drug Combinations; Drug
Interactions; Female; Injections, Intraventricular;
Levodopa (PD/*TO/TU); Macaca mulatta; Motor Activity (DE); Nerve
Tissue Proteins (PD/*TU); Neuroprotective
Agents (PD/*TU); Parkinson Disease, Symptomatic (CI/*DT/PP);
Stereotyped Behavior (DE); Support, Non-U.S.
Gov't; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Publication Type
JOURNAL ARTICLE
ISSN
0364-5134
Country of Publication
UNITED STATES
