During the 1950s, two chemicals that attracted keen interest in understanding normal and abnormal behavior were serotonin and norepinephrine. These neurotransmitters permit nerves to communicate with one another and play a role in regulating our mood. Monoamine oxidase inhibitors (MAOIs) inhibit the action of monoamine oxidase (MAO), an enzyme that breaks down these monoamine neurotransmitters, thereby increasing the brain levels of these neurotransmitters—a process thought to be responsible for their ability to relieve depression.
Iproniazid, the first marketed antidepressant, was toxic to the liver and withdrawn from the market. Appearing several years later, in 1961, the safer MAOIs phenelzine (Nardil) and tranylcypromine (Parnate) are not liver toxic and are still used today. While effective for severe depression, these drugs may cause a sharp drop in blood pressure when the patient suddenly stands (orthostatic hypotension), leading to light-headedness or fainting. More interesting and troubling problems arise when they are taken with other drugs or foods—problems that led to the temporary recall of Parnate in 1964.
Since many of us take more than one drug, awareness of interactions between different drugs is essential. Sometimes one drug increases the effects of another, potentially causing toxicity, while other drugs may reduce or cancel out a second drug’s effects. MAOIs inhibit not only MAO, but also other drugs that are broken down by MAO. The consequences can be fatal.
Far more unusual are drug-food interactions, and here MAOIs are the poster child. Tyramine is a naturally occurring chemical found in generous concentrations in beers and wines (particularly Chianti), fava beans, aged cheeses, beef and chicken liver, pickled and smoked fish and meats, and other delicacies. Normally, these foods present no problems because MAO keeps tyramine levels in check by rapidly breaking it down. When taking an MAOI, however, tyramine levels increase, which can cause blood pressure to rise high enough to cause a stroke! Moreover, the risk of drug and food interactions can persist for up to two weeks after the last MAOI dose is taken.
The MAOIs are now used as backup drugs when patients with severe depression fail to respond to simpler and safer Tofranil-like and Prozac-like drugs.
SEE ALSO Neurotransmitters (1920), Iproniazid (1952), Tofranil and Elavil (1957), Prozac (1987).
Although rarely used today, the MAOIs are about as effective as newer drugs in alleviating depression, but their clinical usefulness as medicines is limited by a wide array of problematic drug-drug and drug-food interactions. Their use is especially troublesome in conjunction with red wines or aged cheeses, both of which contain high concentrations of tyramine.