Tranylcypromine dosing

Phenelzine therapy is initiated at a dose of 15 mg/day. The daily dose can be increased in 15 mg increments on a weekly basis until a therapeutic dose of 45-90mg/day is attained. Tranylcypromine doses are titrated in a similar fashion. Started at 10 mg/day, the daily dose of tranylcypromine can be increased each week by lOmg/day nntil a therapentic dose of 30-40mg/day is achieved. 

With most psychedelics, their activity can probably be considerably enhanced by prior (or possibly concomitant) use of a monoamine oxidase inhibitor (e.g., isocarboxazid (Marplan), nialamide (Niamid), phenelzine (Nardil), and tranylcypromine (Parnate)). Some compounds (e.g., DMT) which have no oral activity, can probably become orally active. These compounds are often prescribed as antidepressants, but it is not a good idea to use them frequently or in large doses. For antidotes to the hallucinogens see Amer. J. Hosp. Pharm. 30,80(1973). 

Several compounds affecting various 5-HT functional parameters (uptake inhibition (fluoxetine), metabolism (tranylcypromine) or synthesis (5-OH tryptophan, 5-HTP)) had no effect on subemetic doses of cisplatin [110]. In fact, tranylcypromine and 5-HTP antagonized emesis of cisplatin. Thus these results would favour an inhibitory role of 5-HT instead of emetogenic. It is conceivable that an excess of 5-HT may desensitize 5-HT3 receptors that may result in a reduced sensitivity to emetogenic stimuli. 

Increased bilirubin levels are caused due to the intake of large doses of such drugs as chloroquine, vitamin K, sulpha-drugs, tetracyclines, paracetamol, nicotinic acid and monoamine oxidase inhibitors (e.g., iproniazid RP 1.0 nialamide RP 1.8 isocarboxazid RP 3.1 phenelzine RP 18 pheniprazine RP31 and tranylcypromine RP 45), where RP designates the Relative Potency based on the tiyptamine potentiation test. The elevated levels are due to hepatic injury, and... 

TRANYLCYPROMINE The usual effective dosage is 30 mg/day in divided doses. If there is no improvement after 2 weeks, increase dosage in 10 mg/day increments of 1 to 3 weeks. Dosage range may be extended to a maximum of 60 mg/day from the usual 30 mg/day. Withdrawal from tranylcypromine should be gradual. 

Drug abuse and dependence There have been reports of drug dependency in patients using doses of tranylcypromine and isocarboxazid significantly in excess of the therapeutic range. 

Cyclopropylamines have been the subject of extensive research over a long period for a variety of reasons. Included in the results of this research was the discovery that certain cyclopropylamines were inhibitors of flavin-containing MAO. Lacking a hydrazide moiety, these compounds were expected to be devoid of liver toxicity, rrans-2-phenylcyclopropylamine (tranylcypromine) (8a), discussed in Section 2.2, appears to be the first cyclopropylamine to be used in clinical trials [109]. Norepinephrine concentrations in the rat brain could be increased by oral administration of lower doses of 8a in comparison to iproniazid [110]. 

In adults, phenelzine, tranylcypromine, and isocarboxazid are rapidly absorbed and have short half-lives, requiring more than once-a-day dosing. For example, the half-life of phenelzine ranges from 1.5 to 4 hours and the half-life for tranylcypromine ranges from 1.54 to 3.15 hours (Mallinger and Smith, 1991). 

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... 

Tranylcypromine, another MAOl, has also been shown to be effective in the treatment of social phobia. Versiani et al. [1988] implemented a 1-year, open trial of tranylcypromine in 32 subjects. Daily doses ranged from 40 to 60 mg. Twenty-nine subjects met criteria for completion of this study. Marked improvement was noted in 62% of patients [18/29], and moderate improvement was shown in 17.2% [5/29]. Six of the 29 subjects were deemed nonresponders [20.6%]. The most commonly cited side effects were orthostatic dizziness [75.5%], insomnia [44.7%], and daytime sleepiness [41.3%]. 

Amsterdam JD Use of high dose tranylcypromine in resistant depression, in Refractory Depression. Edited by Amsterdam JD. NewYork, Raven, 1991,pp 123-130 Amsterdam JD, Berwish N Treatment of refractory depression with combination re-serpine and tricyclic antidepressant therapy. J Clin Psychopharmacol 7 238-242, 1987... 

Amsterdam JD, Berwish N High dose tranylcypromine treatment in refractory depression. Pharmacopsychiatry 22 21-25, 1989... 

Tranylcypromine —10 mg twice daily daily dose range = 20 to 40 mg... 

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. 

This compound, DMCPA, was modeled directly after the structure of DOM, with the 2,5-dimethoxy-4-methyl substitution pattern. Another analogue of tranylcypromine, similarly modeled, is 3,4,5-trimethoxytranylcypromine, ortrans-2-(3,4,5-trimethoxyphenyl)cyclopropylamine (TMT). It has been evaluated at levels of only 13 milligrams orally, and at this dose there were no hints of central activity. 

The first-generation MAO inhibitors phenelzine (19)and tranylcypromine (23) act as substrates for MAOA and MAOB but are converted by the enzyme to highly reactive intermediates that then react irreversibly with the enzyme to cause an irreversible inhibition. of activity. Recovery of MAO activity after exposure to these MAO inhibitors requires the synthesis of new enzyme protein, a process that takes some weeks to completely restore activity (173, 174). A clinical antidepressant response is associated with an inhibition of platelet MAO activity of approximately 80%, and measurement of platelet MAO activity can be used to monitor treatment dose regimes (175). 

Phenelzine, the most frequently prescribed MAOI, has mild to moderate sedating effects. Tranylcypromine may exert a stimulating effect, and insomnia may occur, so the last dose of the day should be administered in the early afternoon. Dose-related impotence and anorgasmia in males and orgasmic inhibition in females have been reported. In addition, fever, myoclonic jerking, and brisk deep tendon reflexes may occur. 

The continuous use of amphetamine causes tolerance, requiring higher doses, and hence there exists a high potential for its abuse. Amphetamine should not be used with a monoamine oxidase A inhibitor such as tranylcypromine, because the chance of inducing hypertension becomes magnified. 

Tranylcypromine, a monoamine oxidase alpha inhibitor (30 mg/day in divided doses), is indicated for the treatment of depression (see Figure 37). 

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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