Sinemet and Side-effects

[Linda Carlton <Carltonl@xxxxxxxxxxx>]

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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