Tyramine pharmacodynamics during combined administration of lazabemide and moclobemide.
The objective of this study was to assess the tyramine pressor sensitivity during combined administration of selective and reversible inhibitors of monoamine oxidase A and B, viz. moclobemide (300 mg b.i.d.) and lazabemide (100 mg b.i.d.), respectively. In part A, 5 healthy male subjects underwent i.v. tyramine pressor tests before (baseline) and during (day 7) combined treatment with both drugs. The tyramine dose was titrated until an increase in systolic blood pressure of 30 mmHg was attained. Subsequently, lazabemide treatment was discontinued and i.v. tyramine pressor tests were again conducted after 2 - 3 days of moclobemide monotreatment. The tyramine pressor sensitivity factor (mean + or - SD) during combined moclobemide and lazabemide treatment was 4.2 + or - 0.9 and during moclobemide monotreatment 3.1 + or - 1.1. In part B, a separate panel of 8 subjects received combined treatment with moclobemide and lazabemide for up to 10 days. Ascending oral doses of tyramine were administered on days 7 - 10 to determine the threshold dose eliciting a 30 mmHg increase in systolic blood pressure. In comparison to baseline the effects of oral tyramine were potentiated by a factor of 13.5 + or - 6.9. The low amount of oral tyramine needed (51 + or - 20 mg) to induce relevant increases in blood pressure indicates that dietary precautions are needed when both MAO-A and B are inhibited by 2 reversible inhibitors.
Dingemanse
J
J
Department of Clinical Pharmacology, F. Hoffmann-La Roche, Basel, Switzerland.
Hussain
Y
Y
Korn
A
A
D000284:Administration, Oral; D018663:Adrenergic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D001549:Benzamides / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D020912:Moclobemide; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010848:Picolinic Acids / Q000494:pharmacology*; D014439:Tyramine / Q000008:administration & dosage / Q000494:pharmacology*
D018663:Adrenergic Agents; D001549:Benzamides; D008996:Monoamine Oxidase Inhibitors; D010848:Picolinic Acids; C059303:lazabemide; D020912:Moclobemide; D014439:Tyramine