The relationship of early studies of monoamine oxidase to present concepts

The development of our understanding of monoamine oxidase (MAO), of its role in the metabolism of amines and of the therapeutic usefulness of MAO inhibitors (MAOIs) have evolved, slowly at times and rapidly at other times, with leaps propelled by new discoveries, new techniques and new insights. Moussa Youdim was one of the major contributors to propulsion of several of these leaps, including the detection of multiple forms of MAO, the descriptions of their properties, active sites and substrates, the use of MAOIs for enhancement of DOPA in treating Parkinson's disease and the evolution of MAO-B inhibitors from mere enzyme inhibitors to lead compounds in the discovery of neuroprotective agents for use in degenerative neurological diseases. Since others will be describing the more recent developments in this field, I thought it would be of interest and instructive to recount the unfolding of our early understanding of MAO, dating from its discovery until the events that first suggested that drugs that inhibit MAO might be neuroprotective. While even the earliest observations about MAO were valid, they were often misinterpreted or confusing, whereas others were predictive of several of our newer concepts of MAO and of side effects encountered in patients treated with MAOIs.