PHARMACODYNAMICS OF MDL 72974A - ABSENCE OF EFFECT ON THE PRESSER RESPONSE TO ORAL TYRAMINE

MDL 72974A, a new irreversible selective inhibitor of monoamine oxidas e (MAO)-B which is not metabolized to amphetamine-like compounds, is c urrently being developed for the treatment of Parkinson's disease. In this double blind, placebo controlled randomized study 24 healthy volu nteers (n = 6/dose) received single oral doses of placebo, 1, 12 or 24 mg of MDL 72974A qd over two weeks. Sensitivity to orally administere d tyramine was determined under fasting conditions before and after dr ug administration and the doses of tyramine yielding a 30 mmHg increas e of SEP (PD30) compared. The 2-fold increase of tyramine sensitivity at end of treatment seen at all MDL 72974A dose levels, however, is wi thin the variability range of the tyramine presser response. MDL 72974 A selectively inhibits MAO-B at doses up to 24 mg orally and has a fav ourable safety profile