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.

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.