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Effect of the putative dopamine D1 agonist and D2 antagonist FCE 23884 on Parkinson's disease.

Abstract
The ergoline derivative FCE 23,884 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 23,884 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 23,884 monotherapy did not affect parkinsonian severity. On the other hand, coadministration of FCE 23,884 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 23,884 in the symptomatic treatment of PD. Although D2 receptor blockade provided by FCE 23,884 antagonizes both the antiparkinson and dyskinesigenic responses to levodopa, the degree of D1 receptor stimulation appears insufficient to ameliorate parkinsonian symptomatology.
AuthorsL V Metman, P J Blanchet, D de Jong, M M Mouradian, T N Chase
JournalMovement disorders : official journal of the Movement Disorder Society (Mov Disord) Vol. 11 Issue 3 Pg. 257-60 (May 1996) ISSN: 0885-3185 [Print] United States
PMID8723141 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiparkinson Agents
  • Dopamine Agonists
  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Ergolines
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • FCE 23884
  • Levodopa
  • Carbidopa
Topics
  • Aged
  • Antiparkinson Agents (adverse effects, therapeutic use)
  • Carbidopa (adverse effects, therapeutic use)
  • Dopamine Agonists (administration & dosage, therapeutic use)
  • Dopamine Antagonists (adverse effects, therapeutic use)
  • Dopamine D2 Receptor Antagonists
  • Double-Blind Method
  • Drug Therapy, Combination
  • Ergolines (adverse effects, therapeutic use)
  • Female
  • Humans
  • Levodopa (adverse effects, therapeutic use)
  • Male
  • Middle Aged
  • Neurologic Examination (drug effects)
  • Parkinson Disease (drug therapy, physiopathology)
  • Receptors, Dopamine D1 (drug effects, physiology)
  • Receptors, Dopamine D2 (physiology)
  • Treatment Outcome

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