Metabolism of Tyramine on Subjects Treated with Different Monoamine Oxidase Inhibitors

Abstract

In the studies presented, the relative extent of tyramine (TYR) deamination to p-hydroxyphenylacidic acid (HPAA) and of TYR conjugation was determined before and during treatment with 5 different MAO inhibitor (MAOI) drugs. Healthy ambulatory subjects were treated p.o. for 2 – 4 weeks. Data were evaluated from (n) subjects. MAOI drugs were: Brofaromine (Brof): 100 – 150 mg/d (9); clorgyline (Clor): 5, 10, 15 mg/d (3); selegiline (Sel): 5, 20 mg/d (6); tranylcypromine (TCP): 20 mg/d (4) and phenelzine (Phen): 30, 45 mg/d (l). After oral doses of TYR causing systolic blood pressure (BP) increases of 30 mm Hg, plasma concentrations of HPAA, conjugated (conj) TYR (after enzymatic deconjugation) and of unconjugated (unc) TYR were determined by HPLC. The area under the plasma level-time curve (AUC) was calculated considering the different TYR doses given (AUCspec). The following results were obtained:

• 1. In l6 untreated subjects une TYR and conj TYR in plasma amount to 0.4 ± 0.2% and 12.5 ± k4.3% of the sum of total TYR + HPAA.

• 2. During subchronic MAO inhibition, the AUCspec of conj TYR after oral TYR administration increases in varying degrees from 12.5% to 92% of the total AUCspec (total TYR + HPAA). This is accompanied by a maximal decrease of AUCspec of HPAA from 87.1% to 8%.

• 3. The following order of increasing potency for inhibiting gastrointestinal MAO could be established: Sel (MAO-B, irreversible), Brof (MAO-A, reversible), Phen (MAO-A+B, irreversible), Clor (MAO-A, irreversible) and TCP (MAO-A+B, partially irreversible).

The results suggest that during inhibition of deamination in the gastrointestinal tract, inactivation by conjugation protects the organism against the pharmacological action of the symphatomimetic amine tyramine.