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 treatm ent of Parkinson's disease patients has traditionally been linked prim arily to dopamine D-1 receptor-mediated mechanisms. However, in MPTP-i nduced parkinsonian monkeys with DID, the administration of selective dopamine D-1 or D-2 agonists will, in the case of D-1 agonists result in similar antiparkinsonian effect but with much less dyskinesia. Thus , once primed, enhanced D-1 neural transmission might in fact benefit DID. In drug-naive MPTP monkeys, the high dyskinetic potential of seve ral selective D-2 agonists and the more favorable outcome on dyskinesi a resulting from the continuous stimulation of D-2 receptors (leading to D-2 receptor down regulation) are important clues suggesting the pr imary role played by D-2 receptor-mediated mechanisms in the dyskinesi a 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.