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A double-blind, placebo-controlled study of the tolerability and effects on platelet MAO-B activity of single oral doses of MDL 72.974A in normal volunteers

  • C. Hinze
  • D. Harland
  • M. Zreika
  • B. Dulery
  • J. Hardenberg
Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 32)

Summary

MDL 72.974A [(E) 4-fluoro-beta-fluorethylene benzene butanamine] has been shown in animal studies, both in vitro and in vivo, to be a potent, selective, enzyme-activated irreversible inhibitor of MAO-B (Zreika et al., 1989). This compound is under clinical development for the treatment of Parkinson’s disease.

In this double blind, randomized, placebo-controlled normal volunteer study the tolerability, effects on platelet MAO-B activity and associated pharmacokinetics of increasing single oral doses of MDL 72.974A (0.1–12 mg) were assessed.

MDL 72.974A was extremely well tolerated and no treatment-related changes in vital signs or the adjectival check-list (EWL-N) occurred. The compound caused significant dose-dependent inhibition of platelet MAO-B activity at all dose levels with a return to baseline values by day 14. The mean (± S.D.) elimination half-life of parent compound was 51 ± 26 min and mean (± S.D.) urinary excretion was 0.54 ± 0.26% of the administered dose. These results, long action on platelet MAO-B and short elimination half-life, demonstrate MDL 72.974A to be a potent, irreversible inhibitor of MAO-B in man.

Keywords

Monoamine Oxidase Single Oral Dose Platelet Rich Plasma Monoamine Oxidase Type Platelet Rich Plasma Sample 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • C. Hinze
    • 1
  • D. Harland
    • 1
  • M. Zreika
    • 1
  • B. Dulery
    • 1
  • J. Hardenberg
    • 1
  1. 1.Department of Clinical ResearchMerrell Dow Research InstituteStrasbourgFrance

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