Medicinal Chemistry of Present and Future MAO-B Inhibitors

Part of the Milestones in Drug Therapy book series (MDT)


The first monoamine oxidase (MAO) inhibitor was described 26 years before the discovery of the enzyme itself. As late as the mid-1900s millions of patients still suffered from tuberculosis. Then, several groups of chemists synthesized molecules with different chemical structures in attempts to create an efficient treatment for this illness. One of these compounds, isonicotinyl hydrazide (isoniazid) was originally synthesized as a necessary intermediary but was later described as an antitu-berculotic agent. This substance was, in essence, the first MAO inhibitor, and it had been described as early as 1912, without regard to its biological activity. Among its monoalkyl derivatives the 2-isopropyl-1-isonicotinyl hydrazide (iproniazid) was the most effective in clinical practice. Its unwanted “lightening” side-effect had been the starting point for pharmacological therapy of depression 1.


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