DOPA-induced "peak dose" dyskinesia: clues implicating D2 receptor-mediated mechanisms using dopaminergic agonists in MPTP monkeys.
Dopa-induced "peak dose" dyskinesia (DID) observed during the treatment of Parkinson's disease patients has traditionally been linked primarily to dopamine D1 receptor-mediated mechanisms. However, in MPTP-induced parkinsonian monkeys with DID, the administration of selective dopamine D1 or D2 agonists will, in the case of D1 agonists result in similar antiparkinsonian effect but with much less dyskinesia. Thus, once primed, enhanced D1 neural transmission might in fact benefit DID. In drug-naive MPTP monkeys, the high dyskinetic potential of several selective D2 agonists and the more favorable outcome on dyskinesia resulting from the continuous stimulation of D2 receptors (leading to D2 receptor down regulation) are important clues suggesting the primary role played by D2 receptor-mediated mechanisms in the dyskinesia priming process. Further clinical studies using drugs selective for the various dopamine receptor subtypes and of different efficacy half-lives are needed to validate our primate data.
Blanchet
P J
PJ
Neurobiology Research Centre, Enfant-Jésus Hospital, Québec City, Canada.
Gomez-Mancilla
B
B
Bédard
P J
PJ
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D004295:Dihydroxyphenylalanine; D018491:Dopamine Agonists / Q000494:pharmacology*; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D000882:Haplorhini; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*
D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D004295:Dihydroxyphenylalanine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine