Influence of food on the tyramine pressor effect during chronic moclobemide treatment of healthy volunteers

Abstract

An open study was carried out to examine the effect of moclobemide, a new antidepressant reversible inhibitor of MAO-A, on the pressor response induced by oral tyramine added to meals of different lipid and protein composition, and to correlate the blood pressure increase in the tyramine test with that obtained during an exercise test. Eight healthy volunteers of both sexes participated in the study. A tyramine sensitivity and an exercise test were performed beforehand. Subjects were included if, under fasting condition, their systolic blood pressure (SBP) increased by more than 30 mmHg after administration of 400 or 600 mg tyramine. Exercise tests were performed to determine the grade of effort that corresponded to a rise in SBP of 30 mmHg. Subjects received moclobemide 600 mg/d. Starting on Day 7, each subject consumed a standardized meal (52 g lipids, 43 g proteins, 86 g carbohydrates) just before taking moclobemide. Tyramine was added to these meals in daily increasing doses of 50, 100, 150...mg until an increase in SBP > or = 30 mmHg was obtained. On moclobemide treatment, an average dose of 250 mg tyramine (range 150-400 mg) increased SBP by 36.6 mmHg. The time to reach peak SBP was longer (175 min) than in the fasting condition before the trial (40.6 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Scientific Opinion on risk based control of biogenic amine formation in fermented foods

“…For the present document, outputs from trials in which tyramine was administrated orally accompanying a meal have been taken into consideration, since they are those most closely reproducing the actual situation of food-borne tyramine intake in comparison with pure tyramine in fasting conditions or intravenous injection. Indeed, it has been reported that increasing mainly lipid but also protein content of the meal significantly reduce the tyramine blood pressor response (Audebert et al, 1992). Bioavailability of tyramine when administered with food or as a dietary constituent seems to drastically be reduced and systematic concentrations are reduced by approximately 2-to 3-fold (Patat et al, 1995;Van den Berg et al, 2003;Azzaro et al, 2006).…”

“…Besides inter-and intraindividual variability, the sensitivity to oral tyramine may also vary depending on the diet composition. Lipids but also proteins seem to significantly reduce the tyramine bioavailability (Audebert et al, 1992), though other substances such as alcohol or other biogenic amines can increase tyramine absorption and thus altering/enhancing its vasopressor effect. This uncertainty leads to both underestimation of the adverse vasopressor effect or to an overestimation of the risk.…”

Pressor response to oral tyramine during co-administration with safinamide in healthy volunteers

“…The study design was based on previous studies (Audebert et al 1992;Patat et al 1995) and is shown in Fig. 1.…”

“…According to literature data, the pressor effect peak was expected within 10-30 min following oral tyramine administration (Audebert et al 1992;Patat et al 1995). After determination of the maximal SBP increase (peak) (ΔSBP), the area under the SBP curve (over baseline) (AUC) and the time of latency (t latency ) were calculated.…”

“…The safety and tolerability of safinamide 300 mg was supported by previous studies (Marzo et al 2004). Since the pressor effect of oral tyramine is reduced during meals, (Audebert et al 1992) and given the tyramine content of a number of food products, the fasting situation was chosen to determine the maximum possible pressor effect and to avoid the variability that could be generated due to interaction with tyramine-containing foods. The present study evaluated the interaction of tyramine, at oral doses of 50-200 mg (range depending on response in absence of treatment), with safinamide 300 mg once daily (o.d.)…”