Phenelzine (sold as Nardil) is a monoamine oxidase inhibitor (MAOI) used as an antidepressant drug.

Mode of action

Phenelzine is a derivative of hydrazine that has a phenylethylamine-like moiety and is similar to normal substrates of MAO. When MAO tries to oxidize phenelzine, this hydrazine-moiety binds covalently to the enzyme, thus inactivating it irreversibly. Phenelzine is a non-selective MAO-inhibitor, thus, it inhibits both MAO-A and MAO-B. Furthermore, phenelzine elevates levels of GABA in the caudate-putamen and nucleus accumbens, primarily through its primary metabolite, PEH (phenylethylidenehydrazine). This may contribute to its anxiolytic properties and superior efficacy in treating severe anxiety.


Phenelzine is administered orally as phenelzine sulfate and it is rapidly absorbed from the gastro-intestinal tract. Although phenelzine has a fairly short half-life, its effect lasts for several weeks, until new functional MAO-enzymes have been produced by the body. Phenelzine is acetylated in the liver and its metabolites are excreted in the urine.

Side effects

Common side effect include orthostatic hypotension, dizziness, headache(without increased blood pressure), fatigue, insomnia, sexual difficulty (esp. ejaculatory dysfunction), urinary hesitancy, chills, carbohydrate cravings, constipation, diarrhea, dryness of mouth, hepatitis (dark urine, skin rash, yellow eyes or skin), parkinsonian syndrome, shakiness or trembling. Most of these side effects dissipate with time and/or careful adjustments of the dosage.

Hypertensive Crises

As with other MAOIs, tyramine-containing foods cause a hypertensive crisis, so users of phenelzine should adhere to certain dietary guidelines, primarily consisting of avoiding certain aged wines and spirits, and certain aged cheeses. The prescribing doctor will advise patients on this issue. The tyramine induced hypertensive crises are estimated to effect only a few percent of the population. It is possible to test patients to see if they are at risk.

Liver Failure

Acute liver failure has been caused by phenelzine when consumed by people with liver damage, advanced age, alcohol consumption, or other drugs, and viral infections.

Nardil formulation

Nardil was changed in late 2003, due to a complete reformulation by Pfizer, who removed many of the excipient ingredients, including the hard coating. It is possible that the current version is not surviving the stomach acid content and therefore not as much is being absorbed into the bloodstream. It is also possible that the machinery used to mix and manufacture Nardil is, since Pfizer acquired the medication, not able to sufficiently blend and mix the medication, making parts or all of some lots irregular in the content of medication delivered to the system.

Many users continue to experience difficulties following this change. The indicated dosage has not been altered by Pfizer, nor did they advise physicians or pharmacies of these changes, yet the recommended dosage seems not to have the desired effect on many. It is believed that, currently, there are some 75,000 to 85,000 people taking Nardil worldwide. The original formulation of Nardil is no longer available. It is now produced by Concord Pharmaceuticals in the UK.

Indicated for

Indicated for:


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