Tyramine reuptake

The modest improvements achieved in selectivity with respect to serotonin reuptake inhibition may also have been achieved with an isoenzyme system. Moclobemide, which was introduced in Sweden, reversibly inhibits monoamine oxidase A (RIMA). It is likely that this eliminates the severe hypertensive drug and food interactions that so severely limit the usefulness of the very effective earlier MAO inhibitors, since tyramine is now metabolized. An additional benefit of such agents may be a lack of cholinergic and cardiovascular effects. 

Fewer adverse effects were reported among moclobemide-treated patients compared with selective serotonin reuptake inhibitor (SSRI)-treated patients. Since moclobemide does not induce orthostatic hypotension, does not possess anticholinergic properties, and is not cardiotoxic, it is very well suited among the MAOIs for the treatment of depression. Moclobemide has limited potential to elicit a hypertensive crisis, because the pressor effect of tyramine from food is only marginally potentiated compared with tranylcypromine. The pressor effect of tyramine is normalized within 3 days of cessation of treatment with moclobemide. The combination of SSRIs and moclobemide has good efficacy in cases of refractory depression, but there is controversy as to whether toxic side-effects such as serotonin syndrome can result from this combination. Currently, more studies are needed before this combination can be recommended. Acute overdose with MAOIs causes agitation, hallucinations, hyperpyrexia, hyperreflexia, convulsions, and death. The most dangerous MAOIs in overdose are the irreversible non-selective MAOIs. T2s-27... 

S5mthesized via tyramine (Fig. 30-26), apparently functions in place of noradrenaline. Note fhe precursor-product relationship between dopamine, noradrenaline, and adrenaline. The synthetic pathways to these neurotransmitters involve decarboxylation and hydroxylahon, types of reacfion imporfanf in formation of other transmitters as well. The most important process for ferminafing fhe acfion of released catecholamine transmitters is reuptake by the neurons. High-affinity uptake systems transport the catecholamine molecules back into the neurons and then into the synaptic vesicles. The uptake is specifically blocked by the drug reserpine (Fig. 25-12).7 The dopamine transporter is a major binding site for cocaine (see Fig. 30-28).7 7-7Si Catecholamine trans-miffers are catabolized by two enzymes. One is the... 

Serotonin reuptake inhibitors Linezolid is a reversible inhibitor of monoamine oxidase and can cause drug-drug interactions when it is combined with monoamine oxidase inhibitors, monoamines such as adrenaline and noradrenaline, tyramine-containing foods, and other serotonergic agents. Several cases of serotonin syndrome have been reported... 

Pharmaceuticals, Inc.) and isocarbazid (Marplan , Validus Pharmaceuticals). They also suppress tyramine uptake. In response to diet-related surges of tyramine, some patients experienced sudden increases in blood pressure that caused fatal brain hemorrhages [51]. Newer antidepressant medications are based upon the inhibition of serotonin reuptake. 

Introduction of reversible MAO-A inhibitors resulted in significantly improved safety during antidepressant therapy. The potential for hypertensive problems is virtually absent because tyramine is able to displace the dmg from the binding site. Furthermore, selectivity for only MAO-A allows for metabolism with MAO-B. The benzamide derivative moclobemide (Fig. 18.24) was launched in 1990 and represents the most commonly used dmg for this particular purpose. Brofaromine, a benzofiiran derivative, has been found to show very similar properties when compared with moclobemide. It also displayed some promising potential as a weak selective serotonin reuptake inhibitor but clinically studies have been abandoned due to lack of corporate interest. 

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