Tyramine and histamine risk assessment related to consumption of dry fermented sausages by the Spanish population.

Tyramine and histamine are the main dietary bioactive amines related to acute adverse health effects. Dry fermented sausages can easily accumulate high levels of these hazards and are frequently consumed in Spain. The present work aims to assess the exposure to tyramine and histamine from the consumption of dry fermented sausages by the Spanish population and to assess the risk to suffer acute health effects from this exposure. A probabilistic estimation of the exposure to these hazards was derived combining probability distributions of these amines in dry fermented sausages (n = 474) and their consumption by the Spanish population. The mean dietary exposure to tyramine and histamine was 6.2 and 1.39 mg/meal, respectively. The risk of suffering hypertensive crisis or histamine intoxication by healthy population due to tyramine or histamine intake, respectively, exclusively from dry fermented sausages, can be considered negligible. For individuals under treatment with MAOI drugs, the probability to surpass the safe threshold dose (6 mg/meal) was estimated as 34%. For patients with histamine intolerance, even the presence of this amine in food is not tolerable and it could be estimated that 7000 individuals per million could be at risk to suffer the related symptoms after consuming dry fermented sausages.

Assessment of the serotonin and norepinephrine reuptake blocking properties of duloxetine in healthy subjects.

Duloxetine is a dual inhibitor of norepinephrine (NE) and serotonin (5-HT) uptake. Initial trials conducted in depressed patients using regimens of 20 mg/day or less did not convincingly demonstrate its efficacy as an antidepressant. The aim of this study was to assess the effects of duloxetine on the 5-HT and NE reuptake processes in healthy human volunteers. Twenty-seven healthy young males without a history of psychiatric disorder were randomly assigned to four groups, each group receiving one of the following daily drug regimens: placebo, clomipramine (a potent 5-HT/NE reuptake blocker) 100 mg/day, duloxetine 20 mg/day, or duloxetine 60 mg/day. In order to assess the NE reuptake process, the pressor response to intravenous tyramine (4 and 6 mg) was measured. Determination of the whole blood 5-HT content was used to evaluate the 5-HT reuptake blockade. These measurements were performed at baseline and repeated after 7 and 14 days of drug intake. Both duloxetine, at doses of 20 to 60 mg/day, and clomipramine significantly interfered with the 5-HT reuptake process, as demonstrated by marked decreases in blood 5-HT concentrations. However, the same doses of duloxetine, unlike clomipramine, failed to impede the usual increase in blood pressure that follows a tyramine intravenous infusion, indicating that clomipramine but not duloxetine blocked NE reuptake. At doses tested in a population of healthy volunteers, duloxetine acted as a selective 5-HT reuptake inhibitor, having no clear effect on the NE reuptake process. Nevertheless, given that the highest dose of duloxetine increased supine systolic blood pressure, it is possible that it represents the threshold regimen for NE reuptake inhibition.

A risk-benefit assessment of moclobemide in the treatment of depressive disorders.

Moclobemide, a novel benzamide, is a reversible inhibitor of monoamine oxidase-A (RIMA). It has been extensively evaluated in the treatment of a wide spectrum of depressive disorders. Comparative studies have shown that the drug is more effective than placebo and as effective as other antidepressants. In terms of efficacy, moclobemide offers no more benefits than do existing agents. On the other hand, moclobemide is better tolerated than tricyclic antidepressants and, unlike irreversible monoamine oxidase inhibitors, has a much lower propensity to cause a 'cheese reaction' (a potentially fatal syndrome caused by an interaction with tyramine-rich foods). These are significant clinical benefits, particularly in elderly patients. Furthermore, moclobemide lacks significant effects on psychomotor performance and cognitive function, has few clinically important drug interactions and is safe on overdose. The drug has a relatively short plasma elimination half-life, a property that allows a change to an alternative agent within 24 hours in cases of nonresponse. Since it is well tolerated, therapeutic dosages can often be achieved from the onset of treatment. These benefits need to be considered against the potential risks of moclobemide therapy. To date, the most significant hazards of therapy appear to arise from drug interactions with clomipramine or selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors, where the occurrence of the serotonin syndrome is potentially fatal. Similarly, in preclinical tests moclobemide has been shown to potentiate the effects of pethidine (meperidine) and dextropropoxyphene, so that combined use of moclobemide is a useful addition to the therapeutic agents used for depressive disorders.(ABSTRACT TRUNCATED AT 250 WORDS)