The Role of Uptake Transporters in Nose to Brain Dopamine Transport: The Characterization of The Role of Dopamine Transporter and Organic Cation ... in Dopamine Transport Across the Nasal Mucosa

Dopamine, involved in the etiology of CNS related disorders such as Parkinson¿s disease, shows poor CNS disposition following oral and IV administration due to its extensive metabolism in the GI tract and poor permeation of the blood brain barrier. However, enhanced CNS uptake of dopamine was observed following intranasal administration. Western blotting and microscopy studies revealed the expression and presence of Dopamine Transporter (DAT) and Organic Cation Transporter-2 (OCT-2) in the nasal mucosa. Bi-directional transport studies demonstrated the role of both transporters in nasal mucosal dopamine transport. Taken together, these studies demonstrated the important role of both DAT and OCT-2 in dopamine uptake across the nasal mucosa. Nasal mucosal metabolism, which was also studied, of dopamine was small. So, nasal mucosal metabolism was not significant and does not limit nasal mucosal permeability of dopamine. The evidence from these studies suggests that enhanced CNS disposition of dopamine following nasal delivery is the result of carrier-mediated transport and is not significantly limited by nasal mucosal metabolism.