Tyramine, monoamine oxidase inhibitors

Normally, dietary tyramine is broken down in the gastrointestinal tract by MAO and is not absorbed. In the presence of MAOI, however, all of its potent sympathomimetic actions are seen. Other side effects of MAOI include excessive CNS stimulation, orthostatic hypotension, weight gain, and in rare cases hepatotoxicity. Because the monoamine oxidase inhibitors exhibit greater toxicity, yet no greater therapeutic response than other, newer agents, clinical use has been markedly curtailed. The primary use for MAOIs is in the treatment of atypical depressions, eg, those associated with increased appetite, phobic anxiety, hypersomnolence, and fatigues, but not melancholia (2). 

Myelosuppression is the major side effect. Nausea, vomiting, and a flulike syndrome occur initially with therapy. Patients must be counseled to avoid tyramine-rich foods because procarbazine is a monoamine oxidase inhibitor. Patients should be provided a list of foods and beverages to avoid to prevent a hypertensive crisis. A disulhramlike reaction can occur with the ingestion of alcohol. 

MAOI (Monoamine Oxidase Inhibitors) will intensify and prolong the effects of NN-DMT, however this is never recommended. Foolish combinations of MAOIs and other drugs can lead to serious health problems and even death. The tryptamines are normally metabolized by an MAO in the body. MAO metabolizes serotonin, norepinephrine, and dopamine. By inhibiting this, MAOIs increase levels of those neurotransmitters. Tyramine will not be metabolized and will cause an increase in tyramine levels in blood. 

Monoamine Oxidase inhibitors (MAOis). There are no controlled studies of MAOIs for the treatment of AN. In addition, the dietary restrictions imposed on patients taking this class of antidepressant and their propensity for lowering blood pressure makes their use in AN inadvisable. In the future, the issue of using MAOis may be reopened with the advent of the so-called reversible MAOis such as moclobemide that apparently do not require a tyramine-restricted diet. 

Monoamine oxidase inhibitors. The monoamine oxidase inhibitors (MAOIs) inhibit the intracellular catabolic enzyme monoamine oxidase. There are two types of monoamine oxidase MAO-A and MAO-B, both of which metabolize tyramine and dopamine. In addition, MAO-A preferentially metabolizes norepinephrine, epinephrine, and serotonin, and MAO-B preferentially metabolizes phenylethylamine (an endogenous amphetamine-like substance) and N-methylhistamine (Ernst, 1996). Some MAOIs are selective for A or B and some are nonselective (mixed). In addition, irreversible MAOIs (e.g., phenelzine, tranylcypromine) are more susceptible to the cheese effect than are the reversible agents (e.g., moclobemide). 

Shulman Kl, Walker SE, MacKenzie S, et al. Dietary restrictions, tyramine, and the use of monoamine oxidase inhibitors. J Clin Psychopharmacol 1989 9 397-402. 

Biosynthesis of catecholamines. The rate-limiting step, conversion of tyrosine to dopa, can be inhibited by metyrosine (K-methyltyrosine). The alternative pathway shown by the dashed arrows has not been found to be of physiologic significance in humans. However, tyramine and octopamine may accumulate in patients treated with monoamine oxidase inhibitors. 

Synergism - a potentiation or prolongation which results in much greater than expected effects. This could involve competitive substrates for an enzyme or receptor, decreased excretion, displaced plasma protein binding, etc. The analgesic propoxyphene (Darvon ) slows down the excretion of ethanol and so increases the depressant effects of the alcohol. Recall the example given earlier of the monoamine oxidase inhibitors used as antidepressants and the tyramine-containing foods which could precipitate a hypertensive crisis. 

Catecholamine neurotransmitters are subsequently inactivated by enzymic methylation of the 3-hydroxyl (via catechol-O-methyltransferase) or by oxidative removal of the amine group via monoamine oxidase. Monoamine oxidase inhibitors are sometimes used to treat depression, and these drugs cause an accumulation of amine neurotransmitters. Under such drug treatment, simple amines such as tyramine in cheese, beans, fish, and yeast extracts are also not metabolized and can cause dangerous potentiation of neurotransmitter activity. 

Cured meats may contain high levels of tyramine, which triggers migraine in susceptible people and causes serious hypertension in patients taking a monoamine oxidase inhibitor such as tranylcypromine. 

Special interest has been focused on the presence of biogenic amines in food plants (45, 90, 360-362), since digestion of food products rich in, e.g., tyramine can induce physiological effects, especially in patients using monoamine oxidase inhibitors as antidepressants (see below). Concentrations of alkaloids reported in food plants are summarized in Table II. 

Isoniazid inhibits monoamine oxidase, and hence reduces tyramine metabolism this effect is enhanced by co-administration of other monoamine oxidase inhibitors... 

Simpson GM, de Leon J. Tyramine and new monoamine oxidase inhibitor drugs. Br J Psychiatry Suppl 1989 6 32-7. 

Monoamine oxidase inhibitors (MAOIs). Some alcoholic (and de-alcoholised) drinks contain tyramine, sufficient to cause a hypertensive crisis in a patient taking a MAOI. 

St. John s wort is a monoamine oxidase inhibitor, and the authors believed that this explained how the concomitant use of a tyramine-rich food with St. John s wort had caused this problem. 

Bieck, P. R., and K. Antonin. 1988. Oral tyramine pressor test and the safety of monoamine oxidase inhibitor drugs Comparison of brofaromine and tranylcypromine in healthy subjects. Journal of Clinical Psychopharmacology 8 237-45. 

There are theoretical drug interactions with caffeine and monoamine oxidase inhibitors. Caffeine could increase risk of cardiovascular events when taken with C. aurantium (54). The case report of MI (45) and several of the Canadian reported adverse events included caffeine (46). Synephrine, tyramine, and octopamine are all substrates of monoamine oxidase (55). Taking a monoamine oxidase inhibitor with C. aurantium could increase concentrations of these sympathomimetics, and thus should be avoided. 

Monoamine oxidase inhibitors are not commonly prescribed to Asians, because many traditional Asian foods, including fermented bean curd, soy sauce, and fermented soybeans, contain relatively high levels of tyramine (a pressor amine), ranging from 0.02 to 43.0 pmol/g (Sung et al. 1986). Because the vast majority of Asians are fast acetylators (Whitford 1978), the metabolism of phenelzine may be increased in Asians, resulting in higher dose requirements than in Caucasians. 

The monoamine oxidase inhibitors are associated with a number of undesirable side effects including weight gain, postural hypotension, sexual dysfunction, and insomnia. The most serious side effect is the risk of tyramine-re-lated hypertensive crisis, often referred to as the "cheese effect," which can be fatal. To avoid this situation patients taking MAOIs must limit their tyramine intake, and the restrictive diet required to accomplish this leads to low patient compliance. A similar interaction occurs when switching patients from MAOI to SSRI therapy, and a minimum 2-week washout period before commencement of SSRI therapy is essential to allow MAO levels to return to normal. The therapeutic effects of the TCAs derive from their inhibition of serotonin and norepinephrine uptake, al-... 

Knoll J, Vizi ES, Somogyi G (1968) Phenylisopropylmethylpropinylamine (E-250), a monoamine oxidase inhibitor antagonizing the effects of tyramine. Arzneimittelf 18 109-112... 

Walker SE, Shulman KI, Tailor SA, Gardner D (1996) Tyramine content of previously restricted foods in monoamine oxidase inhibitor diets. J Clin Psychopharmacol 16 383-388... 

Tyramine-containing foods if taking a monoamine oxidase inhibitor Chemical Elements and Other Industrial Chemicals... 

Monoamine oxidase inhibitors (MAOIs), such as phenelzine, have been used in the management of refractory headache, but their complex adverse-effect profile limits their use to experienced prescribers. Strict adherence to a tyramine-free diet is necessary to avoid potentially life-threatening hypertensive crisis. 

Administered as a single, daily dose on an empty stomach Monoamine oxidase inhibitors drug-food interactions with tyramine-rich foods such as red wines, dark beers, aged cheeses, yogurt may precipitate hypertensive crisis drug interactions tricyclic antidepressants and SSRIs, sympathomimetics disulfiram-like reaction with alcohol... 

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