Cheese reaction

As early as 1961, the first generation of MAO inhibitors (iproniazid, isocarboxazide) were employed for the treatment of Parkinson s disease (PD). However, because of the severe side effects, such as cheese reaction, they were abandoned. The realization that the basal ganglia (extrapyramidal region) of human brain contained mostly MAO-B, which metabolized... 

Cheese Reaction Chemical Chaperone Chemical Library Chemical Neurotransmission Chemoattractant Receptors Chemokine Receptors Chemokines... 

The main problems with early, irreversible MAOIs were adverse interactions with other drugs (notably sympathomimetics, such as ephedrine, phenylpropanolamine and tricyclic antidepressants) and the infamous "cheese reaction". The cheese reaction is a consequence of accumulation of the dietary and trace amine, tyramine, in noradrenergic neurons when MAO is inhibited. Tyramine, which is found in cheese and certain other foods (particularly fermented food products and dried meats), is normally metabolised by MAO in the gut wall and liver and so little ever reaches the systemic circulation. MAOIs, by inactivating this enzymic shield, enable tyramine to reach the bloodstream and eventually to be taken up by the monoamine transporters on serotonergic and noradrenergic neurons. Fike amphetamine, tyramine reduces the pH gradient across the vesicle membrane which, in turn, causes the vesicular transporter to fail. Transmitter that leaks out of the vesicles into the neuronal cytosol cannot be metabolised because... 

Monoamine Oxidase A MAOA Inhibition May induce severe hypertensive crisis (known as the Cheese reaction ) - Centrally mediated side effects such as the serotonin syndrome, dizziness, blurred vision and weakness. 

A newer class of MAO inhibitors, which has entered clinical practice for the treatment of depression, is known as reversible inhibitors of MAO A (RIMAs). This is a very welcome development in new drug therapeutics for depression, because it has the potential of making MAO A inhibition for the treatment of depression much safer. That is, the suicide inhibitors are associated with the dangerous hypertensive episodes mentioned above, which are caused when patients eat food rich in tyramine (such as cheese). This so-called cheese reaction occurs when the tyramine in the diet releases norepinephrine and other sympathomimetic amines (Fig. 5—23). When MAO is inhibited irreversibly, the levels of these amines rise to a dangerous level... 

Enter the reversible MAO inhibitors. If someone eats cheese, tyramine will still release sympathomimetic amines, but these amines will chase the reversible inhibitor off the MAO enzyme, allowing the dangerous amines to be destroyed (Fig. 6—24). This is sort of like having your cake—or cheese—and eating it, too. The reversible MAO inhibitors have the same therapeutic effects as the suicide inhibitors of MAO, but without the likelihood of a cheese reaction if a patient inadvertently takes in otherwise dangerous dietary tyramine. 

Nice huh But most likely wrong. The same text does not fail to mention the so-called cheese reaction , which consists in a sudden rise of blood pressure in patients receiving MAO inhibitors. Cheese - as well as other t5q)es of fermented food, such as salami or summer sausage - is rich in decarboxylation products of amino acids (amines), which are in part responsible for the characteristic flavours. The one of interest here is indeed tyramine. Tyramine acts as an indirect S5mipathomimetic , much in the same way as amphetamine does. It can hardly be held responsible for lowering and increasing the blood pressure at the same... 

Figure 10.22. Hypothetical mechanism of the antihypertensive effect of monoamine inhibitors. This mechanism does not fit the observation of the cheese reaction , in which tyramine contained in fermented food causes hypertensive episodes in patients receiving monoamine oxidase blockers.

A similar example which has been known about for a long time is the so-called cheese reaction which can occur in patients taking... 

DiMartini A. Isoniazid, tricyclics and the cheese reaction . Int Clin Psychopharmacol 1995 I0(3) I97-8. 

The formation of typical cheese flavours during natural ripening processes are not fully understood yet. The majority of reactions last for an extended time period (months) and comprise oxidative, inter- and intramolecular, enzymatic or microbial (cf. blue cheese) reactions. Substrates are partially very reactive milk-based ingredients which are mainly transformed to volatile flavour intensive compounds like esters, methylketones, aldehydes, lactones and sulphur containing products. The effect of enzymes on the flavour enhancement is also not fully understood. By variation of lipase dosage, reaction time and reaction temperature the production of different flavour notes from milk and butterfat is possible. 

No dietary restrictions are required with the doses of rasagiline and selegiline recommended for use in Parkinson s disease. An isolated report describes the cheese reaction in a patient taking selegiline 20 mg daily. Thus, at higher doses of selegiline, restriction of the amount of tyramine in the diet may be necessary. 

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