title: Metabolism of dopamine by the nasal mucosa.
abstract: The nasal route of administration offers several advantages over oral and intravenous administration, including the ability to avoid hepatic first pass metabolism. Dopamine deficiency has been associated with several neurological disorders; it has been shown to have good systemic bioavailability and significant uptake into the CNS following intranasal administration. The purpose of these studies was to investigate the limiting role of mucosal metabolism of dopamine during nasal absorption. In vitro transport and initial rate studies were carried out using nasal mucosal explants to study dopamine permeability and metabolism. Dihydroxyphenylacetic acid (DOPAC) was the only metabolite detected. Monoamine oxidase (MAO), the enzyme responsible for DOPAC formation, was localized to the submucosal region of the nasal explants. The amount of DOPAC formed during the transport studies was less than 0.5% of the initial amount of dopamine placed into the system. Iproniazid, an MAO inhibitor, blocked DOPAC formation but had no effect on dopamine transport. The limited extent of dopamine metabolism compared to its mucosal transport demonstrates that nasal dopamine transport is not significantly reduced by mucosal metabolism and suggests that the nasal route may be promising for the efficient delivery of dopamine to the CNS.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Nagendra V
authors.initials: NV
authors.lastname: Chemuturi
authors.forename: Maureen D
authors.initials: MD
authors.lastname: Donovan
mesh_terms: D019297:2,4-Dinitrophenol / Q000494:pharmacology; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D001682:Biological Availability; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism* / Q000493:pharmacokinetics; D015259:Dopamine Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D007490:Iproniazid / Q000494:pharmacology; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009297:Nasal Mucosa / Q000378:metabolism*; D009924:Organ Culture Techniques; D010879:Piperazines / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet
chemical_list: D015259:Dopamine Agents; D008996:Monoamine Oxidase Inhibitors; D010879:Piperazines; D015102:3,4-Dihydroxyphenylacetic Acid; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D000547:Amantadine; D007490:Iproniazid; D008995:Monoamine Oxidase; D019297:2,4-Dinitrophenol; D004298:Dopamine