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Monoamine oxidase (MAO) inhibitors (MAOI) have a unique history, pharmacology, and toxic syndromes associated with their use. This drug class has fallen in and out of favor with scientists and clinicians over the past several decades. While toxicity from MAOI ingestion is becoming less common due to more limited clinical usage of the traditional nonselective MAOIs, an understanding of MAOI toxicity is fundamental to any clinician who takes care of patients with acute poisoning and xenobiotics overdoses. In this chapter, an overview of clinical manifestations from MAOI toxicity is presented along with an approach to management.

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Monoamine oxidase was discovered in 1928 and named by Zeller when the enzyme was recognized to be capable of metabolizing primary, secondary, and tertiary amines such as tyramine and norepinephrine.126 Subsequently, the monoamine hypothesis postulated depression as a monoamine deficiency state and MAOI drugs were used to target monoamine metabolism for therapeutic benefit. In the early 1950s iproniazid, a drug previously used to treat tuberculosis, was found to produce favorable behavioral side effects. By the mid-1950s, it was demonstrated that iproniazid inhibited MAO, and it then became the first antidepressant used clinically.46

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Another crucial finding in the late 1960s was the existence of two MAO isoforms, each with their own substrate and inhibitor specificity. This paved the way for future 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 at one point were utilized as first-line therapy for depression. In the 1970s, MAOIs were competing with alternative therapies for depression, such as tricyclic antidepressants, which were achieving good clinical results without as many food interactions.

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Intentional MAOI overdose is relatively uncommon and accounts for a dwindling number of annual exposures reported to the American Association of Poison Control Centers. In 2006, there were only 268 exposures reported16 or 0.3% of all antidepressant exposures. Of the reported exposures in 2006, there were only three cases of "major toxic effect" (defined as life-threatening signs or symptoms) and no deaths were reported. Over the past two decades, annual reported MAOI exposures have decreased 34% since 1985 (see Chap. 135). Global MAOI exposure rates most likely mirror the decline occurring in the United States, with the possible exception of exposures to moclobemide, a drug which is not approved by the United States FDA.33

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Chemistry

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Monoamines, also known as biogenic amines, are a group of neuro transmitters including norepinephrine, dopamine, and serotonin that have in common the presence of a single amine group and the ability to be metabolized by MAO. Monoamine oxidase is a flavin-containing enzyme present on the outer mitochondrial membrane of central nervous system (CNS) neurons, hepatocytes, and platelets. In a two-step reaction, MAO catalyzes the oxidative deamination of its various substrates. Importantly, the reaction liberates H2O2...

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