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

J Neural Transm Suppl. 1990;32:203-9. doi: 10.1007/978-3-7091-9113-2_30.

Abstract

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Allyl Compounds*
  • Blood Platelets / drug effects
  • Blood Platelets / enzymology*
  • Blood Pressure / drug effects
  • Butylamines / adverse effects
  • Butylamines / pharmacokinetics
  • Butylamines / pharmacology*
  • Double-Blind Method
  • Electrocardiography
  • Half-Life
  • Heart Rate / drug effects
  • Humans
  • Male
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / adverse effects
  • Monoamine Oxidase Inhibitors / pharmacokinetics
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Reference Values

Substances

  • Allyl Compounds
  • Butylamines
  • Monoamine Oxidase Inhibitors
  • mofegiline
  • Monoamine Oxidase