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Parkinson's disease monotherapy with controlled-release MK-458 (PHNO): double-blind study and comparison to carbidopa/levodopa.

Abstract
The potent and selective dopamine D-2 agonist, MK-458 [PHNO; (+)-4-propyl-9-hydroxynaphthoxazine] was administered as monotherapy to nine patients with Parkinson's disease in a double-blind, placebo-controlled 12-week investigation; ten other patients were randomized to placebo. MK-458 was formulated as a controlled-release preparation, using a hydroxypropyl methylcellulose-lactase (HPMC) matrix. Patients receiving MK-458/HPMC improved on a variety of measures of parkinsonism, compared to their baseline scores; in contrast, only trivial improvement was seen within the placebo group. We subsequently compared the anti-Parkinson response to MK-458/HPMC with the response to chronic carbidopa/levodopa monotherapy in an open label trial. Carbidopa/levodopa improved parkinsonism to a significantly greater degree than MK-458/HPMC. Doses of MK-458 used in these studies (up to 60 mg per day) were substantially higher than those in previously reported preliminary studies of this medication. We conclude that monotherapy with MK-458/HPMC results in a significant anti-Parkinson effect; however, the response falls short of that seen with carbidopa/levodopa.
AuthorsJ E Ahlskog, M D Muenter, P A Bailey, P M Miller
JournalClinical neuropharmacology (Clin Neuropharmacol) Vol. 14 Issue 3 Pg. 214-27 (Jun 1991) ISSN: 0362-5664 [Print] United States
PMID1676932 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Delayed-Action Preparations
  • Dopamine Agents
  • Oxazines
  • naxagolide
  • Levodopa
  • Carbidopa
Topics
  • Adult
  • Aged
  • Carbidopa (therapeutic use)
  • Delayed-Action Preparations
  • Dopamine Agents (administration & dosage, therapeutic use)
  • Double-Blind Method
  • Female
  • Humans
  • Levodopa (therapeutic use)
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Oxazines (administration & dosage, therapeutic use)
  • Parkinson Disease (drug therapy, psychology)

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