Transdermal selegiline: targeted effects on monoamine oxidases in the brain.
BACKGROUND
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.


METHODS
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.


RESULTS
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%.


CONCLUSIONS
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.
Wecker
Lynn
L
Department of Pharmacology and Therapeutics, University of South Florida College of Medicine, Tampa, Florida 33612-4799, USA.
James
Stephanie
S
Copeland
Natalie
N
Pacheco
Mary A
MA
D000279:Administration, Cutaneous; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000201:enzymology; D001923:Brain Chemistry; D004064:Digestive System / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000494:pharmacology*; D013997:Time Factors
D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D008995:Monoamine Oxidase