Potentiation of the pressor effect of oral and intravenous tyramine during administration of the selective MAO-A inhibitor moclobemide in healthy volunteers

Abstract

The interaction between tyramine and the new short-acting and reversible mono amine oxidase inhibitor moclobemide was investigated in a double-blind placebo-controlled study in six healthy volunteers. There were two consecutive study periods of 8 days during which the subjects received moclobemide three x 200 mg daily or placebo. On day 5 of each study period changes in systolic blood pressure (SBP) were determined after incremental intravenous bolus doses of tyramine and on days 6, 7 and 8 changes in SBP were determined after oral tyramine (100, 200 and 300 mg, respectively). Oral tyramine was administered together with a standard breakfast, before which moclobemide had been given. On days 5- 8 blood was taken for determination of blood drug levels. On days 6-8 blood samples were taken before and at 15, 30 and 45 min after tyramine administration for determination of plasma tyramine and plasma norepinephrine concentrations. When SBP had increased by approximately 30 mmHg no further doses of either intravenous or oral tyramine were given. Moclobemide was well tolerated by all subjects. Plasma trough levels of moclobemide were within the therapeutic range. The tyramine induced increases in SBP were greater during moclobemide than during placebo. After intravenous tyramine the dose-response curve for SBP was shifted to the right by a factor of approximately 3. When compared to placebo the pressor response to 100 mg tyramine orally was not significantly different, but the pressor response to the other two doses was enhanced during moclobemide.