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Keywords:

  • Parkinson's disease;
  • Dyskinesias;
  • FCE 23884;
  • D1agonist;
  • D2antagonist

Abstract

The ergoline derivative FCE 23884 acts as a dopamine D1 agonist in untreated parkinsonian animals and as a D2 antagonist in animals whose dopamine system is intact or levodopa treated. To evaluate whether this dual action might benefit patients with Parkinson's disease (PD) who have developed levodopa-induced dyskinesias, the motor effects of FCE 23884 were examined in seven such individuals using a double-blind, placebo-controlled design. At doses up to the maximum tolerated dose (3.5 ± 0.5 mg), FCE 23884 monotherapy did not affect parkinsonian severity. On the other hand, coadministration of FCE 23884 with a mildly dyskinetic dose of levodopa, infused intravenously under steady-state conditions, reduced the antiparkinson response by 54 ± 19% and tended to diminish dyskinesia severity. The results thus fail to suggest any useful role for FCE 23884 in the symptomatic treatment of PD. Although D2 receptor blockade provided by FCE 23884 antgonizes both the antiparkinson and dyskinesigenic responses to levodopa, the degree of D1 receptor stimulation appears insufficient to ameliorate parkinsonian symptomatology.