MODIFICATION OF THE CARDIOVASCULAR EFFECTS OF EPHEDRINE BY THE REVERSIBLE MONOAMINE-OXIDASE-A INHIBITOR MOCLOBEMIDE

Irreversible, nonselective monoamine oxidase (MAO) inhibitors have bee n reported adversely to interact with indirectly acting sympathomimeti c amines present in many cough and cold medicines. This study investig ated the safety and tolerability of concomitant administration to 12 h ealthy subjects of both genders (aged 19-36 years) of ephedrine and mo clobemide, a reversible MAO-A inhibitor. A 2-day, randomized, crossove r administration of placebo or ephedrine (two doses of 50 mg with a 4- h interval) was followed by 9 days open-label dosing with moclobemide, 300 mg b.i.d.. On the last 2 days of moclobemide dosing, the randomiz ed crossover treatment Of ephedrine and placebo was repeated. No subje ct was withdrawn from the study for tolerability reasons. Moclobemide treatment, however, increased the incidence of adverse events elicited by ephedrine, particularly palpitations and headache. The pharmacodyn amic interaction between the two drugs was quantified by calculation o f the area under the effect-time course (AUE) for systolic (SEP) and d iastolic blood pressure (DBP) and heart rate (HR). The difference in A UE between monotreatment with ephedrine and placebo was statistically significant for all three vital signs. Moclobemide potentiated the eff ect of ephedrine by a median factor of 3.2 for SEP, 3.8 for DBP, and 0 .6 for HR. Ephedrine had no significant influence on the plasma concen trations of moclobemide or its metabolites. In conclusion, the combine d use of moclobemide and high doses of sympathomimetic drugs should be approached with caution.