Daily transdermal administration of selegiline to guinea-pigs preferentially inhibits monoamine oxidase activity in brain when compared with intestinal and hepatic tissues.
Selegiline has been formulated in an acrylic polymer adhesive mixture to be employed as a constant release topical patch for daily transdermal administration. Application of this selegiline transdermal system (STS) to guinea-pigs resulted in an average delivery of 1.185 mg selegiline/cm(2) patch/24 h. STS dose-response curves were generated by altering patch size (cm(2)). A transdermal dose range was identified which inhibited guinea-pig brain monoamine oxidase-B (MAO-B) by greater than 95% yet provided for a dose-dependent inhibition of monoamine oxidase-A (MAO-A) activity. The ID50 for inhibition of MAO-A activity in response to a 21-day daily regimen with transdermal selegiline was approximately 7.5-fold lower for cortical and striatal brain regions compared with that obtained for duodenum; hepatic MAO-A was unaffected following the same dosing regimen. By contrast, orally administered selegiline inhibited brain and duodenal MAO-A to the same extent, and generated a shallower dose-inhibition curve for brain MAO-A inhibition. In addition, transdermal delivery was approximately 6-8-times more potent than oral selegiline for the inhibition of brain MAO-A activity. It is concluded that daily transdermal selegiline administration may provide therapeutic advantages over oral treatment, based on its preferential, dose-dependent inhibition of brain vs peripheral MAO-A activity.
Mawhinney
Michael
M
Department of Pharmacology, West Virginia University School of Medicine, Morgantown, WV 26506, USA. mmawhinney@hsc.wvu.edu
Cole
Dennis
D
Azzaro
Albert J
AJ
D000279:Administration, Cutaneous; D000818:Animals; D001921:Brain / Q000201:enzymology*; D004064:Digestive System / Q000201:enzymology; D006168:Guinea Pigs; D008099:Liver / Q000201:enzymology; D008297:Male; D008995:Monoamine Oxidase / Q000032:analysis / Q000494:pharmacology*; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D012642:Selegiline / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*
D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D008995:Monoamine Oxidase