Interaction of MAO inhibitors and dietary tyramine: a new experimental model in the conscious rat.
The aim of this study was to assess a new model for tyramine-induced pressor effects in the rat. The predictivity of the test is improved by simulating the real clinical situations where tyramine is ingested with food and beverages containing the amine. The pressor effect was investigated after oral administration of tyramine in a feed preparation or in a water solution by continuously recording blood pressure just above the aorta junction via a left-carotid catheter. The response was quantified by measurement of peak systolic blood pressure and as the percentage of tyramine-sensitive rats (TSR) in which the maximal pressor response to the amine was higher than 30 mm Hg (clinical risk threshold). Tyramine elicited, after oral administration (by gavage), a statistically significant dose-dependent increase in blood pressure from the dose of 10 mg/kg in solution (i.e. 23 +/- 3 mm Hg, N = 36) and 40 mg/kg in feed preparation (i.e., 20 +/- 2 mm Hg, N = 26). Almost all rats showed a systolic blood pressor increase higher than 30 mm Hg after oral administration of tyramine at a dose of 80 mg/kg p.o. in solution (TSR = 96%). Administration of tyramine in food (80 mg/kg) significantly delayed the time of the peak blood pressure (13 +/- 2 min instead of 7 +/- 0.5 min in solution, p < .001). Under these conditions, the tyramine threshold dose of TYR 30 (dose inducing an average response equivalent to the clinical risk threshold) was 14 mg/kg p.o. in solution and 67 mg/kg p.o. in feed preparation, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Fankhauser
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C
Synthelabo Recherche (L.E.R.S.), Preclinical Research Department, Rueil-Malmaison, France.
Charieras
T
T
Caille
D
D
Rovei
V
V
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010624:Phenelzine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000378:metabolism*; D014439:Tyramine / Q000008:administration & dosage / Q000494:pharmacology
D008996:Monoamine Oxidase Inhibitors; D010624:Phenelzine; D014439:Tyramine