Daily transdermal administration of selegiline to guinea-pigs preferentially inhibits monoamine oxidase activity in brain when compared with intestinal and hepatic tissues

ABSTRACT 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/cm2 patch/24 h. STS dose‐response curves were generated by altering patch size (cm2). 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.