Effect of Moclobemide, a New Reversible Monoamine Oxidase Inhibitor, on Absorption and Pressor Effect of Tyramine

We determined in healthy subjects the pressor effect and the plasma level of free tyramine in response to intravenous and oral tyramine doses before and after therapeutic doses (3 X 100 mg/day) of moclobemide, a new reversible, preferential type A monoamine oxidase (MAO) inhibitor. In fasting subjects moclobemide increased the pressor effect of intravenously and orally administered tyramine; the tyramine dose-pressor curve was shifted to the left by factors of 2.4 and 4.1, respectively. No increase in systolic blood pressure occurred at free plasma tyramine concentrations lower than 70 ng/ml before, and 20 ng/ml after, moclobemide. Peak plasma tyramine concentrations increased dose-dependently after oral tyramine; after moclobemide similar peak plasma concentrations of tyramine were obtained with 2.6 times smaller doses of tyramine. Thus, the potentiation by moclobemide of the pressor effect of oral tyramine appears to be due to inhibition of tyramine first-pass metabolism, as well as to inhibition of tyramine catabolism by MAO within adrenergic nerve terminals. The peak concentrations of free tyramine in plasma and the concomitant increase of systolic blood pressure were significantly (p less than 0.01) smaller when tyramine was administered with a meal (before or after moclobemide) than when given with tap water. We conclude that at doses of 3 X 100 mg/day moclobemide induces only a mild potentiation of the pressor effect of tyramine. This potentiation is virtually absent under natural conditions when tyramine is given with a meal.