Selegiline transdermal

Paroxetine (Paxil, Paxil CR) Phenelzine (Nardil) Selegiline transdermal (Emsam)... 

VandenBerg CM, Blob LF, Gerrick G, et al. Blood pressure response produced by a tyramine-enriched meal following multiple dose administration of a 20 cm 120 mg selegiline transdermal system (STS) in healthy male volunteers. 40th Annual Meeting NCDEU, Boca Raton, Florida, 2000(abst). 

Phenelzine Blockade of MAO-A and MAO-B (phenelzine, nonselective) MAO-B irreversible selective MAO-B inhibition (low dose selegiline) Transdermal absorption of selegiline achieves levels that inhibit MAO-A Major depression unresponsive to other drugs Very slow elimination Toxicity Hypotension, insomnia Interactions Hypertensive crisis with tyramine, other indirect sympathomimetics serotonin syndrome with serotonergic agents, meperidine... 

Pae CU et al Selegiline transdermal system Current awareness and promise. Prog Neuropsychopharmacol Biol Psychiatry 1997 31(6) 1153. 

Amsterdam, J. D. (2003), A double-blind, placebo-controlled trial of the safety and efficacy of selegiline transdermal system without dietary restrictions in patients with major depressive disorder,/. Clin. Psychiatry, 64(2), 208-214. 

Azzaro, AJ. et al., Pharmacokinetics and absolute bioavailability of selegiline following treatment of healthy subjects with the selegiline transdermal system (6mg/24h) A comparison with oral selegiline capsules, J. Clin. Pharmacol., 47, 1256, 2007. 

Barrett JS, Hochadel TJ, Morales RJ, Rdial S, DeWitt KE, Wats i SK, Damow J, Azzaro AJ, DiSanto AR. Presscr response to tyramine after sir le 24-hour a f>lication of a selegiline transdermal system in healthy m Ae. JClmPh umacol( 99T) 37,238-47. 

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. 

Accordingto the FDA-approved prescribing information for the transdermal selegiline patch, patients receiving the 6 mg/24 hour dose are not required to modify their diet. However, patients receiving the 9 or 12 mg/24 hour dose are still required to follow the dietary restrictions similar to the other monoamine oxidase inhibitors (MAOIs). 

MAOIs had been reserved as a last line of treatment, used only when other classes of antidepressant drugs had failed, because of the mentioned potentially lethal dietary and drug interactions. However, in 2006 a patch form of the drug selegiline, called Emsam, was approved for use by the FDA. When applied transdermally the drug does... 

Patkar AA, Pae CU, Zarzar M. Transdermal selegiline. Drugs Today 2007 43(6) 361-77. 

The MAOIs are as effective as the heterocyclic antidepressants and the newer agents, such as the SSRIs. However, at least two forms of life-threatening toxicity (hepatotoxicity and dietary tyramine-induced hypertensive crisis ) have been associated with their chronic use. For this reason, the MAOIs are not considered first-line agents in the treatment of depression. They are generally reserved for treatment of depressions that resist therapeutic trials of the newer, safer antidepressants. However, a new transdermal formulation of selegiline undergoing clinical trials demonstrates antidepressant efficacy without concerns of liver toxicity or dietary tyramine-induced hypertension. 

Given the unique efficacy of MAOIs, there have been several attempts to develop kinder and gentler versions. A transdermal form of selegiline is one promising approach. Another approach is the development of selective and reversible MAOIs (180). 

Selegiline is an irreversible but relatively selective inhibitor of MAO-B. An oral preparation is currently marketed as a treatment for Parkinson s disease. An oral dose produces meaningful inhibition of MAO-B but not MAO-A. The concept behind the transdermal patch is to preferentially deliver more selegiline to the brain than to the liver such that meaningful inhibition of both MAO-A and MAO-B is achieved in the brain but only MAO-B inhibition is achieved in the liver. The... 

The MAO-B inhibitor, l-deprenyl, has been approved by the FDA for use in Parkinson s disease. At the lower dose range, it does not interact with tyramine. As mentioned earlier, there is preliminary evidence of antidepressant efficacy for a transdermal delivery system for selegiline. This formulation does not interact with tyramine to produce a hypertensive crisis (181). 

Because of the prominent first-pass effects and their tendency to inhibit MAO in the gut (resulting in tyramine pressor effects), alternative routes of administration are being developed. For example, selegiline is available in both transdermal and sublingual forms that bypass both gut and liver. These routes decrease the risk of food interactions and provide substantially increased bioavailability. 

In a single-blind, placebo-controlled, within-subject, non-randomized, crossover study in 12 cocaine-dependent subjects, intravenous cocaine (20 mg and 40 mg) was evaluated before and during transdermal selegiline (20 mg), a selective inhibitor of monoamine oxidase B... 

Houtsmuller EJ, Notes LD, Newton T, Van Sluis N, Chiang N, Elkashef A, Bigelow GE. Transdermal selegiline and intravenous cocaine safety and interactions. Psychopharmacology 2004 172 31 10. 

Sacktor N, Schifitto G, McDermott MP, Marder K, McArthur JC, Kieburtz K (2000) Transdermal selegiline in HIV-associated cognitive impairment Pilot, placebo-controlled study. Neurology 54 233-235. 

Bodkin JA, Amsterdam JD (2002) Transdermal selegiline in major depression a double-blind, placebo-controlled, parallel-group study in outpatients. Am J Psychiatry 159 1869-1875... 

NOTE Most of the drugs are hydrochloride salts, but SURMONTIL and LUVOX are maleates CELEXA is a hydrobromide, and remeron is a free-base. Selegiline is approved for early Parkinson s disease, but may have antidepressant effects, especially at daily doses 20 mg, and is under investigation for administration by transdermal patch. 

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