Tranylcypromine Selegiline

Current MAOIs include the hydrazine derivatives phenelzine and isocarboxazid and the non-hydrazines tranylcypromine, selegiline, and moclobemide (the latter is not available in the USA). The hydrazines and tranylcypromine bind irreversibly and nonselectively with MAO-A and -B, whereas other MAOIs may have more selective or reversible properties. Some of the MAOIs such as tranylcypromine resemble amphetamine in chemical structure, whereas other MAOIs such as selegiline have amphetamine-like metabolites. As a result, these MAOIs tend to have substantial CNS-stimulating effects. 

Isocarboxazid (Marplan) Moclobemide (Aurorix, Manerix, Moclodura ) Phenelzine (Nardil) Tranylcypromine Selegiline (Selegiline, Eldepryl)... 

Monoamine Oxidase Inhibitors Isocarboxazid, Phenelzine, Tranylcypromine, Selegiline, Moclobemide... 

Acute treatment with nonselective MAO inhibitors (iproniazid, tranylcypromine, phenelzine), as a consequence of inhibiting both forms of the enzyme, increase, brain levels of all monoamines (phenylethylamine, tryptamine, methylhistamine aminergic neurotransmitters (dopamine, noradr enaline, adrenaline and serotonin). By contrast MAO-A inhibitors (clorgyline) increase serotonin and noradrenaline, while MAO-B inhibitors (selegiline, rasagiline) increase brain levels... 

Isocarboxizid, phenelzine, selegiline, tranylcypromine, moclobemide, clorgiline, and linezolid... 

The monoamine oxidase inhibitors (MAOIs) phenelzine and tranylcypromine increase the concentrations of NE, 5-HT, and DA within the neuronal synapse through inhibition of the monoamine oxidase (MAO) enzyme system. Both drugs are nonselective inhibitors of MAO-A and MAO-B. Selegiline is available as a transdermal patch for treatment of major depression. It inhibits MAO-A and MAO-B in the brain, but has reduced effects on MAO-A in the gut. 

These mediators probably play significant roles in CNS functions consistent with the stimulant effects of MAO inhibitors on mood and psychomotor drive and their use as antidepressants in the treatment of depression (A). Tranylcypromine is used to treat particular forms of depressive illness as a covalently bound suicide substrate, it causes long-lasting inhibition of both MAO isozymes, (MAOa, MAOb). Moclobemide reversibly inhibits MAOa and is also used as an antidepressant. The MAOb inhibitor selegiline (deprenyl) retards the cat-obolism of dopamine, an effect used in the treatment of parkinsonism (p. 188). 

In the United States, the three MAOIS available for the treatment of psychiatric conditions are phenelzine (Nardil), tranylcypromine (Parnate), and isocarboxazid (Marplan). All three agents have indications for adult major depression (>16 years old) and, more specifically, atypical depression (anergia, hypersomnia, hy-perphagia, somatization, and anxiety symptoms). Although not indicated for anxiety, the MAOIs can also be particularly helpful in treatment of these disorders. Selegiline or L-deprenyl (Eldepryl) is also available in the United States and indicated for symptoms of Parkinson s disease and depression. 

Preliminary studies suggest that MAOIs are effective in juvenile and adult ADHD. In a controlled trial of clorygline (MAOI-A) and tranylcypromine sulfate (mixed), Zametkin et al. (1985) reported a significant reduction in ADHD symptoms with minimal adverse effects. Eeigin et al. (1996) conducted a controlled trial of 10 mg of selegiline (which at low doses is a specific MAOI-B) in children with ADHD and Tourette s syndrome. Selegiline was well tolerated and was associated... 

The different MAOIs are metabolized via different pathways but tend to have extensive first-pass effects that may substantially decrease bioavailability. Tranylcypromine is ring hydroxylated and /V-acetylated, whereas acetylation appears to be a minor pathway for phenelzine. Selegiline is /V-demethylated and then hydroxylated. The MAOIs are well absorbed from the gastrointestinal tract. 

MAOIs are classified by their specificity for MAO-A or -B and whether their effects are reversible or irreversible. Phenelzine and tranylcypromine are examples of irreversible, nonselective MAOIs. Moclobemide is a reversible and selective inhibitor of MAO-A but is not available in the USA. Moclobemide can be displaced from MAO-A by tyramine, and this mitigates the risk of food interactions. In contrast, selegiline is an irreversible MAO-B-specific agent at low doses. Selegiline is useful in the treatment of Parkinson s disease at these low doses, but at higher doses it becomes a nonselective MAOI similar to other agents. 

These two classes of drugs are subject to life-threatening interactions (e.g., mania, convulsions, hypertension, heart arrythmias) with monoamine oxidase (MAO) inhibitors, such as isocarboxazide, phenelzine, selegiline, and tranylcypromine, because they inhibit the metabolism of serotonin and sympathomimetic amines (19,120). This interaction is one of the earliest toxic drug-drug interactions to be recognized however, these interactions are not often observed because the MAO inhibitors are now used sparingly. 

Monamine oxidase inhibitors (MAOIs) Phenelzine (Nardil) Selegiline transdermal (Emsam) Tranylcypromine (Parnate)... 

Inhibitors Modobcmidc Tranylcypromine Phenelzine iproniazid Selegiline... 

Phenelzine (Nardil) and tranylcypromine (Parnate) are the two most common MAOIs. Two newer MAOIs are being studied to evaluate their clinical use both have a reduced risk of hypertensive reaction. Selegiline (Deprenyl) is an MAO-B inhibitor (inhibits type B MAO) that is used in the treatment of Parkinson s disease and may be especially useful for treating depression in patients with Parkinson s. Meclobe-mide, a reversible MAO-A inhibitor, is currently used in Europe and Canada and may soon be available in this country. 

Most MAOIs are irreversible and the effects take weeks to stabilize. Chemically, they fall into a number of groups, including hydrazines, such as pheneizine and iproniazid, propargylamines, such as pargyline, chlorgyline and selegiline, and cyclopropylamines, such as tranylcypromine. A reversible inhibitor that may be safer under some circumstances is moclobemide. The use of MAOIs has declined and tricyclics and the SSRIs are being used more. See antidepressants. 

Clinically important, potentially hazardous interactions with dexibuprofen, isocarboxazid, MAO inhibitors, phenelzine, selegiline, St John s wort, sumatriptan, tramadol, tranylcypromine, trazodone... 

Clinically important, potentially hazardous interactions with antihypertensives, dexamethasone, ephedra, furazolidone, guanethidine, guarana, MAO inhibitors, methyldopa, oxprenolol, phenelzine, phenylpropanolamine, selegiline, tranylcypromine, tricyclic antidepressants... 

Clinically important, potentially hazardous interactions with alprazolam, amphetamines, astemizole, clarithromycin, clozapine, desipramine, dexibuprofen, dextroamphetamine, diethylpropion, droperidol, duloxetine, erythromycin, haloperidol, imipramine, isocarboxazid, linezolid, lithium, MAO inhibitors, mazindol, meperidine, methamphetamine, midazolam, moclobemide, nortriptyline, phendimetrazine, phenelzine, phentermine, phenylpropanolamine, phenytoin, pimozide, pseudoephedrine, selegiline, serotonin agonists, sibutramine, St John s wort, sumatriptan, sympathomimetics, tramadol, tranylcypromine, trazodone, tricyclic antidepressants, troleandomycin, tryptophan, zolmitriptan... 

MAOIs can be classified into two groups the irreversible (older) MAOIs such as Parnate (tranylcypromine) and Nardil (phenelzine), and the reversible (newer) drugs such as Manerix (moclobemide) and Deprenyl (selegiline). Older MAOIs have more side effects associated with them since their action is less specific than newer MAOIs. 

DA agonists levodopa, bromocriptine, ropinirole, pramipexole, selegiline AAAD inhibitor carbidopa M-blockers benztropine, trihexiphenidyl MAOIs phenelzine, tranylcypromine TCAs amitriptyline, imipramine, clomipramine SSRIs fluoxetine, paroxetine, sertraline Others bupropion, mirtazapine, nefazodone, trazodone... 

SELECTIVE MAO-B INHIBITORS Two isozymes of MAO (MAO-A and MAO-B) oxidize monoamines and both are present in the periphery and GI tract MAO-B is the predominant form in the striatum and is responsible for most of the oxidative metabolism of dopamine in the brain. At low-to-moderate doses (10 mg/day or less), selegiline (eldepryl) selectively and irreversibly inhibits MAO-B. Unlike nonspecific inhibitors of MAO (e.g., phenelzine, tranylcypromine, isocarboxazid), selegiline does not inhibit peripheral metabolism of catecholamines and can be taken safely with levodopa. Selegihne does not cause the lethal potentiation of indirectly acting sympathomimetic amines such as dietary tyramine. Doses of selegiline higher than 10 mg daily can produce inhibition of MAO-A and should be avoided. 

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