SELECTIVE INHIBITORS OF MONOAMINE-OXIDASE .2. ARYLAMIDE SAR

Monoamine oxidase (MAO) exists in two forms distinguishable by substra te specificity. Inhibition of MAO A is believed to be responsible for the antidepressant activity of MAO inhibitors. A group of N-arylacetam ides are highly specific inhibitors of MAO A, some with IC50 values in the 10-100 nM range. The requirements for high activity and specifici ty include a nearly linear tricyclic aromatic portion but a larger and a smaller central ring component. The amide group, which is best acet amido, is optimally placed para to the smaller central group. The size and shape of the aromatic moiety appear to be the major influence on activity and specificity for MAO A.