Most monoamine oxidase (MAO) inhibitors are used primarily for severe depression resistant to other antidepressant drugs, but are also used to treat phobias and anxiety disorders. First-generation MAO inhibitors include isocarboxazid (Marplan), phenelzine (Nardil), and tranylcypromine (Parnate). Newer-generation MAO inhibitors with lower toxicity include selegiline (Eldepryl, Emsam, Zelapar) and rasagiline (Azilect), also used in the treatment of Parkinson's disease, and moclobemide (Aurorix, Manerix), a much less toxic antidepressant that is available in many countries, but not in the United States. Multiple other MAO inhibitors are marketed outside the United States to treat depression, anxiety disorders, Parkinson's disease, and bacterial infections. Serious toxicity from MAO inhibitors occurs with overdose or owing to interactions with certain other drugs or foods (Table II–41).
++ Table Graphic Jump Location TABLE II–41.MONOAMINE OXIDASE INHIBITOR INTERACTIONSa ||Download (.pdf) TABLE II–41. MONOAMINE OXIDASE INHIBITOR INTERACTIONSa
|Drugs ||Foods |
|Amphetamines ||Metaraminol ||Beer |
|Buspirone ||Methyldopa ||Broad bean pods and fava beans |
|Clomipramine ||Methylphenidate ||Cheese (natural or aged) |
|Cocaine ||Paroxetine ||Chicken liver |
|Dextromethorphan ||Phenylephrine ||Pickled herring |
|Ephedrine ||Phenylpropanolamine ||Smoked, pickled, or aged meats |
|Fluvoxamine ||Reserpine ||Snails |
|Fluoxetine ||Sertraline ||Spoiled or bacterially contaminated foods |
|Guanethidine ||Tramadol || |
|L-Dopa ||Trazodone ||Summer sausage |
|LSD (lysergic acid diethylamide) ||Tryptophan ||Wine (red) |
|Venlafaxine ||Yeast (dietary supplement and Marmite) |
Drugs of other classes may have MAO-inhibiting activity, including procarbazine (Matulane), linezolid (Zyvox), the recreational drugs paramethoxyamphetamine (PMA) and methylenedioxymethamphetamine (MDMA, "ecstasy" [Amphetamines]), and methylene blue. The popular herbal product used for depression, St. John's wort (Hypericum perforatum), appears to act in part as an MAO inhibitor and has been implicated in interactions with medications such as selective serotonin reuptake inhibitors (SSRIs). A number of other plant products containing tryptamines, harmines, and hydroxyindole have also been shown to have MAO-inhibiting activity, including such popular herbals as resveratrol piperine (found in pepper), ginkgo biloba, ginseng, and berberine.
MECHANISM OF TOXICITY
MAO inhibitors inactivate MAO, an enzyme responsible for degradation of catecholamines within CNS neurons. MAO is an enzyme with two major subtypes, MAO-A and MAO-B. MAO-A is also found in the liver and intestinal wall, where it metabolizes tyramine and therefore limits its entry into the systemic circulation.
Toxicity results from the release of excessive neuronal stores of vasoactive amines, inhibition of metabolism of catecholamines, or absorption of large amounts of dietary tyramine (which in turn releases catecholamines from neurons).
Selegiline was developed as a selective MAO-B inhibitor that does not require a restrictive diet. (MAO-B selectivity is lost at doses above 20 g/d; thus, overdose with selegiline resembles that of the older MAO inhibitors.) Antidepressant treatment with transdermal selegiline (Emsam) is feasible because higher doses of selegiline reach the CNS owing to bypass of hepatic first-pass metabolism. A recent study showed that at low transdermal doses (6 ...