A 35-year-old woman with treatment-resistant depression is started on a MAO-B selective inhibitor as augmentation, and later develops hypertensive crisis after eating aged cheese. The mechanism is:

• A Selegiline directly activates trace amine-associated receptor 1 (TAAR1), amplifying tyramine's pressor effect
• B Selegiline inhibits catechol-O-methyltransferase (COMT), reducing tyramine degradation
• C MAO-B inhibition prevents tyramine conversion to dopamine, diverting it to norepinephrine synthesis
• D At high doses, selegiline (MAO-B inhibitor) loses its selectivity and inhibits MAO-A in the gut and liver, allowing dietary tyramine to enter systemic circulation and displace norepinephrine from vesicles ✓

Explanation

At conventional doses (10 mg/day), selegiline is selective for MAO-B, which predominantly catabolises dopamine. Dietary tyramine is normally degraded by intestinal and hepatic MAO-A. At higher doses used in depression (e.g., transdermal selegiline >9 mg/24h, or oral doses >10 mg), selectivity is lost and MAO-A is inhibited. Without intestinal/hepatic MAO-A, tyramine in aged cheese, wine, and fermented foods is absorbed intact, enters the circulation, and causes massive norepinephrine displacement ('tyramine pressor response') resulting in hypertensive crisis. This is the 'cheese effect' — a dose-dependent loss of selectivity, not an intrinsic MAO-B interaction.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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