Can our knowledge of monoamine oxidase (MAO) help in the design of better MAO inhibitors?

Abstract

This paper presents a rapid overview of the mechanism by which monoamine oxidase (MAO) catalyzes the deamination of its substrates, and highlights the stereoselective nature of the active site of the enzyme. With the help of a few selected examples it is also discussed which structural factors are thought to have a preponderant influence on the affinity and selectivity of molecules towards the active site of either form of MAO. From the currently available data on the enzyme and its inhibition, it clearly appears that new MAO inhibitors, of whatever type, could be easily designed by structural modulation of molecules already found to have MAO inhibitory properties. As to whether better MAO inhibitors could be envisaged, it is suggested that MAO inhibition might be advantageously combined with other pharmacological properties for the treatment of pathological conditions, such as stroke and epilepsy, to the occurrence of which MAO activity might contribute. The rationale of this approach is presented.