Tyramine, reaction with

Most of the adverse reactions to selegiline are related to actions of increased levels of dopamine, as discussed earlier. At recommended doses, and unlike the nonselective MAO inhibitors used in the treatment of depression, selegiline has little effect on MAO-A and therefore generally does not cause the hypertension associated with the ingestion of tyramine-enriched foods (see Chapter 20). However, at doses higher than those usually recommended, MAO-A may be inhibited, which increases the risk of a tyramine reaction. 

Another approach is to develop selective and reversible MAOIs. The goal again is to produce agents with a minimal risk of tyramine reactions and thus markedly diminish the need for the dietary restrictions that have plagued the use of nonselective and irreversible A, B inhibitors. Collaborative clinical trials of the reversible inhibitors of monoamine oxidase A (RIMAs) in Europe have included more than 2,000 patients, many hospitalized for more severe, endogenous depressive episodes (183). In comparison trials with the TCAs, the onset of effect with RIMAs was also more rapid in some cases. 

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... 

Despite warnings, it seems doubtful that the weak MAO-inhibito-ry properties of procarbazine can under normal circumstances cause a hypertensive reaction with tyramine or other sympathomimetics. 

The reaction with amines is formulated in Figure 1. Polyfunctional molecules react completely under the usual conditions 0,N-bis-Dns-tyramine, JV,N-bis-Dns-histamine, tri-Dns-spermidine, tetra-Dns-spermine and tri-Dns-norepinephrine are the products when excess of the reagent is used. Amino acids react first with the amino group. The Dns-amino acids tend, however, to react with excess Dns-Cl to form mixed anhydrides, especially at high pH. These tend to break down to CO, Dns-NH2, the aldehyde with one carbon less lhan the parent amino acid and dimethylaminonapththalene-1-sulphonic acid [18] (Figure 2). y-Amino acids under the same conditions form the y-lactams. [17,19-21]. 

Iridoid alkaloids are formed by reaction of nitrogen-free iridoids with ammonia or amines. Gentiopicroside, for instance, is converted to gentianin in a nonenzyma-tic reaction in the presence of ammonia (Fig. 105). The iridoid alkaloids of Valeriana officinalis (Fig. 102) may be formed in a similar reaction with the participation of tyramine (D 22.1.1). 

One serious adverse reaction associated with the use of the MAOIs is hypertensive crisis (extremely high blood pressure), which may occur when foods containing tyramine (an amino acid present in some foods) are eaten (see Home Care Checklist Avoiding Drug Food Interactions With MAOIs). 

M AO Is. The MAOIs are not widely used because of their potential for serious adverse reactions. Fhtients receiving MAOIs require strict dietary control because foods containing tyramine should not be eaten because of the danger of a hypertensive crisis. (See Home Care Checklist Avoiding Drug-Food Interactions With MAOIs). 

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... 

Ethanol DOES NOT interact with MAOIs however, tyramine may be a component of some aged alcoholic drinks, such as red wines or tap beers if a reaction occurs, hypertension and a pounding headache are the most likely symptoms usually white wine is fine (in moderation) and most widely available domestic canned beers do not contain significant amounts of tyramine. 

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. 

This group of enzymes catalyzes the oxidation of amines. Amine oxidase [EC 1.4.3.4], a flavin-containing enzyme (also known as monoamine oxidase, tyramine oxidase, tyraminase, or adrenalin oxidase) catalyzes the reaction of an organic amine R—CH2—NH2) with dioxygen... 

From L-tyrosine, or alternatively from L-phenylalanine, there is one further alkaloid biosynthesis pathway. This is the galanthamine pathway (Figure 38). Galanthamine synthesizes with tyramine, norbelladine, lycorine, crinine, N-demethylnarwedine and Al-demethylgalanthamine. Schiff base and reduction reaction, oxidative coupling and enzyme NADPH and SAM activity occur in this pathway. Schiff base is a reaction for the ehmination of water in formation with the C—N bonds process. 

Procarbazine may potentiate the effects of tranquilizers and hypnotics. Hypertensive episodes can result if procarbazine is administered simultaneously with adrenomimetic drugs or with tyramine-containing foods. Rarely, a reaction to alcohol similar to that provoked by disulfiram may occur. 

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