Tyramine potentiation during treatment with MAO inhibitors: brofaromine and moclobemide vs irreversible inhibitors.
Healthy ambulatory subjects were treated p.o. for 2 to 4 weeks with 6 different MAO inhibitors (MAOI). MAOI drugs were given to (n) subjects. Brofaromine (Brof): 100-150 mg/d (39); moclobemide (Mocl): 450 mg/d (8); clorgyline (Clor): 5, 10, 15 mg/d (5); selegiline (Sel): 5, 20 mg/d (7); phenelzine (Phen): 30, 45, 60 mg/d (6); tranylcypromine (TCP): 20 mg/d (12). Pressor responsiveness to oral tyramine (TYR) was assessed before, during, and after treatment. In unmedicated subjects (Cont), doses of TYR to raise systolic blood pressure by at least 30 mm Hg (PD30), ranged between 200 and 800 mg. During treatment with MAOIs, the PD30 decreased. The median effective doses (ED 50) of TYR were: Cont (n = 55): 437 mg; Sel, 20 mg/d: 96 mg; Mocl 450 mg/d: 63 mg; Brof: 100-150 mg/d: 44 mg; Phen, 60 mg/d: 33 mg; Clor, 10 mg/d: 43 mg; CP: 8 mg. Pressor responsiveness to oral TYR normalized within 3 d (Mocl), 8 d (Brof), and 30 d (TCP). After Phen, in 2 subjects the potentiation persisted for 2 and 4 weeks, in 4 volunteers for 8 and more weeks. After Clor, only one of 4 subjects reached 83% of his early pressor sensitivity within 15 weeks. The results suggest that the two reversible MAO-A inhibitors Mocl and Brof may lessen the liability to TYR-related hypertensive reactions.
Bieck
P R
PR
Human Pharmacology Institute, Ciba-Geigy, Tübingen, Federal Republic of Germany.
Antonin
K H
KH
D000328:Adult; D001549:Benzamides / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008297:Male; D020912:Moclobemide; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D013997:Time Factors; D014439:Tyramine / Q000494:pharmacology*
D001549:Benzamides; D008996:Monoamine Oxidase Inhibitors; D010880:Piperidines; C038213:brofaromine; D020912:Moclobemide; D014439:Tyramine