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HISTORY AND EPIDEMIOLOGY

Monoamine oxidase inhibitors (MAOIs) have a unique history, pharmacology, and toxic syndrome. Although toxicity from MAOI ingestion is becoming less common because of more limited clinical usage of the traditional nonselective MAOIs, an understanding of MAOI toxicity is fundamental to any clinician who cares for patients with acute poisoning.

Monoamine oxidase (MAO) was discovered in 1928 and named by Zeller when the enzyme was recognized to metabolize primary, secondary, and tertiary amines such as tyramine and norepinephrine.132 Subsequently, the “monoamine hypothesis” postulated depression as a condition of monoamine deficiency, and MAOIs targeted monoamine metabolism for therapeutic benefit. In the early 1950s, iproniazid, a drug previously used to treat tuberculosis, was found to produce favorable behavioral effects. By the mid-1950s, it was demonstrated that iproniazid inhibited MAO, and it then became the first antidepressant used clinically.22

In the late 1960s, two MAO isoforms were identified, each with substrate and inhibitor specificity. This determination led to the development of selective MAOIs in attempts to minimize the many food and drug interactions that occur with the traditional nonselective MAOIs. Nonselective MAOIs proved to be potent and efficient antidepressants and became the first-line therapy for depression. In the 1970s, alternative therapies for depression, such as the tricyclic antidepressants, were developed and achieved clinical success without as many food and drug interactions.

Intentional MAOI overdose is relatively uncommon and accounts for a dwindling number of annual exposures reported to the American Association of Poison Control Centers. From 2011 to 2015, there was a decreasing trend in the number of exposures with fewer than 100 exposures reported in 2015 (Chap. 130), representing less than 1% of all antidepressant exposures. Of the reported exposures in 2010, there were only five cases of “major toxic effect” (defined as life-threatening signs or symptoms), and no deaths were reported. Over the past 2 decades, annual reported MAOI exposures have decreased 34% since 1985 (Chap. 130). Global MAOI exposure rates declined in proportion with the United States, with the possible exception of exposures to moclobemide, a drug not approved by the US Food and Drug Administration (FDA).33

Many authors recommend the prescription of nonselective MAOIs only for resistant or atypical depression with prominent neurovegetative symptoms.30 However, selective and reversible MAOIs are the subject of renewed clinical applicability and basic science research interest. Monoamine oxidase-B selective xenobiotics, such as selegiline, are widely used for the treatment of Parkinson disease. Reversible inhibitors of MAO, such as moclobemide, are used in Europe for depression, phobias, anxiety, and other select indications.130 Current applicability of a new generation of experimental MAOIs is being investigated as neuroprotective xenobiotics for a variety of neurodegenerative diseases.132

PHARMACOLOGY

Chemistry

Monoamines, also known as biogenic amines, include the catecholamines (epinephrine, norepinephrine, dopamine, tyrosine), indolamines (serotonin, melatonin), and some ...

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