Selective inhibitors of monoamine oxidase. 2. Arylamide SAR.

Monoamine oxidase (MAO) exists in two forms distinguishable by substrate specificity. Inhibition of MAO A is believed to be responsible for the antidepressant activity of MAO inhibitors. A group of N-arylacetamides are highly specific inhibitors of MAO A, some with IC50 values in the 10-100 nM range. The requirements for high activity and specificity include a nearly linear tricyclic aromatic portion but a larger and a smaller central ring component. The amide group, which is best acetamido, 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.