Switching from levodopa to the long-acting dopamine D2/D3 agonist piribedil reduces the expression of dyskinesia while maintaining effective motor activity in MPTP-treated primates.
BACKGROUND
The control of motor complications following dopaminergic medication in late-stage Parkinson disease remains problematic.


OBJECTIVE
We now investigate the potential of oral administration of the long-acting dopamine D2/D3 agonist piribedil to decrease the expression of dyskinesia induced by prior exposure to levodopa in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-treated primates.


METHODS
MPTP-treated common marmosets were treated with equieffective doses of levodopa (10.0-12.5 mg/kg PO, twice daily) or piribedil (3.0-4.0 mg/kg PO, once daily) for 30 days and then switched to the alternative treatment for a further 35 days.


RESULTS
Levodopa administration markedly improved motor function, but dyskinesia rapidly appeared and intensified as treatment progressed. Administration of piribedil produced a similar reversal of MPTP-induced motor deficits but with comparatively mild dyskinesia. On switching from levodopa to piribedil, the intensity of dyskinesia decreased without altering the improvement in motor deficits. However, on switching from piribedil to levodopa, the rapid increase in dyskinesia despite the improvement in motor function being maintained suggests that piribedil also primes for but does not markedly express dyskinesia.


CONCLUSIONS
The study confirms the low dyskinesia expression resulting from piribedil treatment compared with an equieffective dose of levodopa. Importantly, the results show that switching from levodopa to piribedil rapidly results in a sustained decrease in dyskinesia intensity.
Smith
Lance A
LA
Neurodegenerative Diseases Research Group, School of Biomedical and Health Sciences, King's College, London, UK.
Jackson
Michael J
MJ
Johnston
Louisa
L
Kuoppamaki
Mikko
M
Rose
Sarah
S
Al-Barghouthy
Ghassan
G
Del Signore
Susanna
S
Jenner
Peter
P
D000818:Animals; D002144:Callithrix; D018491:Dopamine Agonists / Q000008:administration & dosage*; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D007980:Levodopa / Q000008:administration & dosage*; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D010891:Piribedil / Q000008:administration & dosage*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000502:physiology
D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D007980:Levodopa; D010891:Piribedil