Levels of dopamine in blood and brain following nasal administration to rats.
The aim of this study was to investigate the levels of [(3)H]dopamine in blood, the cerebrospinal fluid (CSF) and brain tissue samples in rats and to find out whether the drug is transferred along the olfactory pathway to the central nervous system following nasal administration. [(3)H]Dopamine (50 microCi) was given to male Sprague-Dawley rats either intravenously or nasally to the right nostril. For the absorption study, blood samples were withdrawn from the carotid artery. The CSF samples were taken by cisternal puncture and then brain tissue samples were excised. The presence of unchanged dopamine in the samples was ascertained using thin layer chromatography (TLC). The radioactivity in the samples was measured using liquid scintillation. The greatest amount of the total radioactivity absorbed from the nasal mucosa into the systemic circulation was observed at the first sampling point 15 min after administration. The bioavailability of the total radioactivity was 68+/-30%. The uptake of [(3)H]dopamine in the brain was significantly higher 30 min after nasal administration than after intravenous administration (P<0.01). TLC data showed that approximately 59%, 14% and 68% of the radioactivity in the olfactory bulb, CSF and olfactory mucosa, respectively, coeluted with dopamine. In conclusion, these results show that unchanged dopamine is transferred into the olfactory bulb via the olfactory pathway in rats.
Dahlin
M
M
Department of Pharmacy, Division of Pharmaceutics, Biomedical Centre, Box 580, Uppsala University, SE-751 23, Uppsala, Sweden.
Jansson
B
B
Björk
E
E
D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D004298:Dopamine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D009830:Olfactory Bulb / Q000378:metabolism; D051381:Rats
D004298:Dopamine