Exposure-Topology Engineering for Functional Dissociation Between Peripheral and Central MAO Activity

Treatment-resistant depression (TRD) remains a major unmet clinical challenge despite the availability of multiple antidepressant classes. This conceptual framework introduces exposure-topology engineering as a translational strategy for compartment-selective modulation of centrally active neuropharmacological agents. The proposed approach explores how controlled modulation of early free-fraction exposure dynamics may enable functional dissociation between peripheral monoamine oxidase inhibition and central therapeutic activity. Using selegiline as a representative model, this work discusses potential implications for treatment-resistant depression, CNS therapeutics, spatial pharmacokinetics, and next-generation neuropharmacological strategies. Associated intellectual property is currently under patent application. Keywords: Translational Neuropharmacology, CNS Therapeutics, Treatment-Resistant Depression, Exposure-Topology Engineering, Spatial Pharmacokinetics, Selegiline.