Oral tyramine pressor test and the safety of monoamine oxidase inhibitor drugs: comparison of brofaromine and tranylcypromine in healthy subjects.
The pressor effect of orally administered tyramine (TYR) has been evaluated in 124 tests of 49 healthy unmedicated volunteers, in 99 tests of 29 subjects treated with the reversible selective monoamine oxidase (MAO) A inhibitor brofaromine (BROF), and in 73 tests of 12 subjects treated with tranylcypromine (TCP). In unmedicated subjects, pressor doses of TYR to raise systolic blood pressure (BP) by 30 mm Hg (PD30) ranged between 200 and 800 mg of TYR. There was no correlation of PD30 with sex, age, or weight. In repeated tests, the intraindividual coefficient of variation of the PD30 (+/- SD) was 10 +/- 9%. During treatment for 8 to 16 days with the two MAO inhibitors (MAOIs) BROF and TCP, seven-fold and 56-fold increases of TYR pressor sensitivity were estimated. A significant correlation was found between the individual PD30 before and during MAO inhibition with BROF. Cheese with a pressor content equal to the PD30 of TYR raised the systolic BP in only three of 10 volunteers during BROF inconsistently by not more than 20 mm. Therefore, the probability of "cheese reactions" during treatment with this reversible MAOI seems to be small. For complete normalization of oral pressor responsiveness, delays of 8 and 30 days after the last doses of BROF and TCP, respectively, are needed. The total incidence of systolic BP elevations by more than 60 mm Hg was 13% in a total of 296 oral tests given to 49 subjects. This incidence of easily controllable hypertensive reactions is outweighed by the importance of the test as predictor of clinical risks for drugs with TYR potentiating effects.
Bieck
P R
PR
Human Pharmacology Institute CIBA-Geigy, Tübingen, Federal Republic of Germany.
Antonin
K H
KH
D000293:Adolescent; D000328:Adult; D000931:Antidotes / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000009:adverse effects*; D010646:Phentolamine / Q000494:pharmacology; D010880:Piperidines / Q000009:adverse effects*; D014191:Tranylcypromine / Q000009:adverse effects*; D014439:Tyramine
D000931:Antidotes; D008996:Monoamine Oxidase Inhibitors; D010880:Piperidines; D014191:Tranylcypromine; C038213:brofaromine; D014439:Tyramine; D010646:Phentolamine