Monoamine oxidase inhibition by tranylcypromine: assessment in human volunteers

The inhibition of monoamine oxidase (MAO) by tranylcypromine was studied in 6 healthy volunteers given increasing doses of 10, 15, 20 and 25 mg/day over a 4-week period. Measurements were made of urinary tryptamine excretion, blood pressure response to tyramine (TY) and norepinephrine (NE), and subjective self-rating. A significant increase in urinary tryptamine, indicating the onset of MAO inhibition, occurred in all 6 subjects once the cumulative dose of 40 mg TC had been administered. Thereafter, urinary tryptamine increased up to 7-fold, dose-dependently with large interindividual variation (78 +/- 27 to 549 +/- 252 microgram/g creatinine). Within 4 days after stopping the drug, control values were reached again. The assessment of TY potentiation by comparison of equieffective doses (S dose) became up to 10 times more sensitive when both the height and the duration of the increase in systolic blood pressure (S AUC) were taken into account. The increases in tyramine sensitivity found with the highest cumulative doses of TC (5.4 +/- 0.8 mg/kg; n =6) were S dose from 8-16 and S AUC from 28-162, respectively. The pharmacodynamic half-life (Pd 1/2) of TC approximated a mean first fast Pd 1/2 of 1.3 d and a slower phase of 14.2 d. During treatment with the highest TC dose, resting blood pressure was significantly elevated from 120 to 128 mm Hg, and the pressor sensitivity to NE (S NE) in 4 of the 6 subjects rose, the mean was 1.7 (n = 6). In 3 volunteers NE sensitivity was normalized within 4 days after stopping TC. There was a significant correlation between increasing vigilance with TC dose in 5 volunteers (r = 0.81, n = 15, p less than 0.01). It is concluded that combination of the results of several tests has provided reliable information about the onset, extent and duration of MAO inhibition in healthy volunteers.