A Brief History of the MAOIs

The enzyme monoamine oxidase (MAO) is responsible for the destruction of various monoamine neurotransmitters including serotonin, noradrenaline, and dopamine. As humans age, levels of monoamine oxidase increase, reducing the availability of neurotransmitters and theoretically increasing the risk of disorders such as depression and Parkinson’s disease (10). Drugs that inhibit MAO increase concentrations of monoamines and can treat depression (11). In order to gain an appreciation of where l-deprenyl fits within the grand scheme of psychopharmacology, it’s important to look at the origins of the MAOIs.

In 1952, Crane reported the “psychiatric side-effects” of the tuberculosis drug, iproniazid (1). Iproniazid, which was later found to inhibit the enzyme monoamine oxidase (MAO), produced“psychic energizing” euphoria in tuberculosis patients (2, 3). This led to considerable interest in the use of monoamine oxidase inhibitors (MAOIs) for the treatment of depression, narcolepsy, social phobia, and schizophrenia.

With regard to schizophrenia, Lauer observed that when patients were given iproniazid along with the serotonin precursor L-tryptophan, they became livelier and more willing to engage interpersonally. It appeared that by inhibiting the breakdown of serotonin while simultaneously increasing its production with precursors enabled a more robust response
(4). Such an observation had relevance to Parkinson’s disease, where patients suffer from a deficit of dopamine. If the breakdown of dopamine could be slowed with the use of an MAOI, the effects of the precursor drug L-dopa might be enhanced. While MAOI’s appeared to have weak anti-Parkinson’s effects on their own due to their dopamine sparing activity, when combined with L-dopa, a hypertensive crisis often ensued (6).