Levels of dopamine in blood and brain following nasal administration to rats

被引:84
作者
Dahlin, M [1 ]
Jansson, B [1 ]
Björk, E [1 ]
机构
[1] Uppsala Univ, Biomed Ctr, Div Pharmaceut, Dept Pharm, SE-75123 Uppsala, Sweden
关键词
nasal administrations; dopamine; rat; olfactory pathway; cerebrospinal fluid (CSF); brain targeting;
D O I
10.1016/S0928-0987(01)00151-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The aim of this study was to investigate the levels of [H-3]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 mu Ci) 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Sprague-Dawley rats either intravenously or nasally to the right nostril, For the absorption study, blood samples were withdrawn from the carotid artery.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 A [H-3]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. (c) 2001 Elsevier Science BY. All rights reserved.
引用
收藏
页码:75 / 80
页数:6
相关论文
共 30 条
[1]   DEGRADABLE STARCH MICROSPHERES AS A NASAL DELIVERY SYSTEM FOR INSULIN [J].
BJORK, E ;
EDMAN, P .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1988, 47 (1-3) :233-238
[2]  
Chen Xue-Qing, 1998, J Alzheimers Dis, V1, P35
[3]   A rapid assay for tyrosine hydroxylase activity, an indicator of chronic stress in laboratory and domestic animals [J].
Chobotská, K ;
Arnold, M ;
Werner, P ;
Pliska, V .
BIOLOGICAL CHEMISTRY, 1998, 379 (01) :59-63
[4]   The distribution of local anesthetics into the CSF following intranasal administration [J].
Chou, KJ ;
Donovan, MD .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1998, 168 (02) :137-145
[5]  
Chow HHS, 1999, J PHARM SCI, V88, P754
[6]   Transfer of dopamine in the olfactory pathway following nasal administration in mice [J].
Dahlin, M ;
Bergman, U ;
Jansson, B ;
Bjork, E ;
Brittebo, E .
PHARMACEUTICAL RESEARCH, 2000, 17 (06) :737-742
[7]   Nasal absorption of (S)-UH-301 and its transport into the cerebrospinal fluid of rats [J].
Dahlin, M ;
Björk, E .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2000, 195 (1-2) :197-205
[8]   Delivery of I-125-NGF to the brain via the olfactory route [J].
Frey, WH ;
Liu, J ;
Chen, XQ ;
Thorne, RG ;
Fawcett, JR ;
Ala, TA ;
Rahman, YE .
DRUG DELIVERY, 1997, 4 (02) :87-92
[9]   FUNCTIONAL-PROPERTIES OF VERTEBRATE OLFACTORY RECEPTOR NEURONS [J].
GETCHELL, TV .
PHYSIOLOGICAL REVIEWS, 1986, 66 (03) :772-818
[10]  
GEURKINK N, 1983, J ALLERGY CLIN IMMUN, V72, P123, DOI 10.1016/0091-6749(83)90518-3