The current concept of dyskinesia is that pulsatile stimulation of D-1 or D-2 receptors by L-DOPA orshort-acting dopamine agonists is more likely to induce dyskinesia compared to long-acting drugs producingmore continuous receptor stimulation. We now investigate the ability of two mixed D-1/D-2 agonists,namely pergolide (long-acting) and apomorphine (short-acting), to induce dyskinesia in drugnaı¨ve MPTP-lesioned primates, compared to L-DOPA. Adult common marmosets (Callithrix jacchus)were lesioned with MPTP (2 mg/kg/day sc for 5 days) and subsequently treated with equieffectiveantiparkinsonian doses of L-DOPA, apomorphine, or pergolide for 28 days. L-DOPA, apomorphine, andpergolide reversed the MPTP-induced motor deficits to the same degree with no difference in peak response. L-DOPA and apomorphine had a rapid onset of action and short duration of effect producing apulsatile motor response, while pergolide had a slow onset and long-lasting activity producing a continuousprofile of motor stimulation. L-DOPA rapidly induced dyskinesia that increased markedly in severityand frequency over the course of the study, impairing normal motor activity by day 20. Dyskinesiain animals treated with pergolide or apomorphine increased steadily, reaching mild to moderate severitybut remaining significantly less marked than that produced by L-DOPA. There was no difference in theintensity of dyskinesia produced by apomorphine and pergolide. These data suggest that factors otherthan duration of drug action may be important in the induction of dyskinesia but support the use ofdopamine agonists in early Parkinson’s disease, as a means of delaying L-DOPA therapy and reducing therisk of developing dyskinesia.
|Numero di pagine||12|
|Stato di pubblicazione||Published - 2003|
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