Monoamine oxidase inhibition by phenelzine and brofaromine in healthy volunteers.
The two monoamine oxidase (MAO) inhibitors phenelzine and brofaromine given for 2 to 3 weeks were compared in six volunteers. Blood pressure sensitivity to intravenous tyramine increased 2.6-fold during phenelzine (60 mg/day) and 4.8-fold during brofaromine, whereas sensitivity to oral tyramine increased more during phenelzine (15.7-fold vs 8.5-fold). After withdrawal of phenelzine, pressor sensitivity to oral tyramine returned to control values within 2 and for more than 8 weeks. Relative bioavailability of conjugated tyramine was elevated sixfold by brofaromine and 11.6-fold by phenelzine. Urinary elimination of tryptamine increased during phenelzine and brofaromine to 12.7-fold and threefold, respectively. 3-Methoxy-4-hydroxyphenylglycol (MHPG) and 3-methoxy-4-hydroxymandelic acid (VMA) excretion decreased during brofaromine significantly by 72% and 49%, respectively. The nonsignificant decrease of MHPG excretion and the increase of intravenous tyramine pressor sensitivity caused by phenelzine are significantly related. The data suggest that the selective reversible MAO-A inhibitor brofaromine has a larger therapeutic safety than phenelzine.
Bieck
P R
PR
Human Pharmacology Institute, Ciba-Geigy, Tübingen, F.R.G.
Firkusny
L
L
Schick
C
C
Antonin
K H
KH
Nilsson
E
E
Schulz
R
R
Schwenk
M
M
Wollmann
H
H
D000328:Adult; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000652:urine; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D010624:Phenelzine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D014363:Tryptamines / Q000652:urine; D014439:Tyramine / Q000493:pharmacokinetics / Q000494:pharmacology; D014642:Vanilmandelic Acid / Q000652:urine
D008996:Monoamine Oxidase Inhibitors; D010880:Piperidines; D014363:Tryptamines; C030820:tryptamine; D008734:Methoxyhydroxyphenylglycol; D014642:Vanilmandelic Acid; C038213:brofaromine; D010624:Phenelzine; D014439:Tyramine