Transdermal selegiline: targeted effects on monoamine oxidases in the brain.
ABSTRACT The oral administration of monoamine oxidase (MAO) inhibitors has the potential to cause a hypertensive reaction after the ingestion of tyramine-containing compounds. Because transdermal drug administration bypasses gastrointestinal absorption, it is possible that inhibition of MAO-A in brain may be achieved without enzyme inhibition in the gastrointestinal system, thereby eliminating the possibility of this drug interaction. These studies determined whether the transdermal administration of selegiline has differential effects on MAOs in brain versus the gastrointestinal system.
Rats were exposed to various doses of selegiline via a transdermal patch for up to 30 days, and MAO-A and MAO-B activities were determined in brain regions and gastrointestinal tissue.
In all brain regions, transdermal selegiline, at doses that produced maximal MAO-B inhibition, led to a dose- and time-dependent MAO-A inhibition. The inhibition of MAOs in gastrointestinal tissue was less than that in brain, and doses that produced maximal MAO-A inhibition in brain inhibited MAO-A in gastrointestinal tissue by only 30%-40%.
Results suggest that transdermal selegiline preferentially inhibits MAO-A in brain relative to the gastrointestinal system. As a consequence, transdermal selegiline should be devoid of the potential to cause a hypertensive reaction after the ingestion of tyramine-containing compounds.
Article: Léo Edmond Marion (1899-1979)
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ABSTRACT: In the past year, there has been a slow but steady trickle of new psychotropic agents into the United States market. In general, there are more novel formulations of older agents than there are novel agents. For example, a transdermal form of selegiline has become available that circumvents some of the problems with traditional monoamine oxidase inhibitors. There are new formulations of zol-pidem and carbamazepine that may offer more practical routes of administration for some patients. In addition, there are new hypnot-ics including eszopiclone and ramelteon. In this educational review, the application, dosing, and monitoring of these newer medications is reviewed along with all previously introduced medications.
- New England Journal of Medicine 11/2005; 353(17):1819-34. DOI:10.1056/NEJMra050730 · 54.42 Impact Factor