Ability of nitrobenzylthioinosine to cross the blood-brain barrier in rats
Identifieur interne : 003D90 ( Main/Exploration ); précédent : 003D89; suivant : 003D91Ability of nitrobenzylthioinosine to cross the blood-brain barrier in rats
Auteurs : Christopher M. Anderson [Canada] ; Daniel S. Sitar [Canada] ; Fiona E. Parkinson [Canada]Source :
- Neuroscience Letters [ 0304-3940 ] ; 1996.
English descriptors
- KwdEn :
- Animals, Binding, Competitive, Blood-Brain Barrier, Brain (metabolism), Injections, Intraperitoneal, Injections, Intravenous, Male, Rats, Rats, Sprague-Dawley, Sucrose (pharmacokinetics), Thioinosine (analogs & derivatives), Thioinosine (cerebrospinal fluid), Thioinosine (metabolism), Thioinosine (pharmacokinetics), Thioinosine (pharmacology), Thionucleotides (pharmacology).
- MESH :
- chemical , analogs & derivatives : Thioinosine.
- chemical , cerebrospinal fluid : Thioinosine.
- chemical , metabolism : Thioinosine.
- chemical , pharmacokinetics : Sucrose, Thioinosine.
- metabolism : Brain.
- chemical , pharmacology : Thioinosine, Thionucleotides.
- Animals, Binding, Competitive, Blood-Brain Barrier, Injections, Intraperitoneal, Injections, Intravenous, Male, Rats, Rats, Sprague-Dawley.
Abstract
Nucleoside transport inhibitors that cross the blood-brain barrier may be able to potentiate the neuroprotective effects of adenosine. We tested whether nitrobenzylthioinosine (NBMPR) crosses the blood-brain barrier in three types of experiments. First, intravenous injection of [3H]NBMPR and [14C]sucrose was performed. Brain volume of distribution and brain delivery were greater for [3H]NBMPR than for [14C]sucrose. Second, rats were injected intraperitoneally with NBMPR 5′-monophosphate (NBMPR-P), a prodrug form of NBMPR, or vehicle. Perchloric acid extracts of brains from rats treated with NBMPR-P inhibited [3H]NBMPR binding in competition binding assays nearly 3-fold more than extracts from brains of vehicle-treated animals. Third, cerebrospinal fluid (CSF) extracted from rats treated with NBMPR-P (10 mg/kg i.p.) contained 24.1 ± 4.4 nM NBMPR while levels were undetectable in CSF from vehicle-treated rats. From these data, we conclude that NBMPR crosses the blood-brain barrier.
Url:
DOI: 10.1016/S0304-3940(96)13220-1
Affiliations:
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We tested whether nitrobenzylthioinosine (NBMPR) crosses the blood-brain barrier in three types of experiments. First, intravenous injection of [3H]NBMPR and [14C]sucrose was performed. Brain volume of distribution and brain delivery were greater for [3H]NBMPR than for [14C]sucrose. Second, rats were injected intraperitoneally with NBMPR 5′-monophosphate (NBMPR-P), a prodrug form of NBMPR, or vehicle. Perchloric acid extracts of brains from rats treated with NBMPR-P inhibited [3H]NBMPR binding in competition binding assays nearly 3-fold more than extracts from brains of vehicle-treated animals. Third, cerebrospinal fluid (CSF) extracted from rats treated with NBMPR-P (10 mg/kg i.p.) contained 24.1 ± 4.4 nM NBMPR while levels were undetectable in CSF from vehicle-treated rats. From these data, we conclude that NBMPR crosses the blood-brain barrier.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Manitoba</li></region><settlement><li>Winnipeg</li></settlement><orgName><li>Université du Manitoba</li></orgName></list><tree><country name="Canada"><region name="Manitoba"><name sortKey="Anderson, Christopher M" sort="Anderson, Christopher M" uniqKey="Anderson C" first="Christopher M." last="Anderson">Christopher M. Anderson</name></region><name sortKey="Parkinson, Fiona E" sort="Parkinson, Fiona E" uniqKey="Parkinson F" first="Fiona E." last="Parkinson">Fiona E. Parkinson</name><name sortKey="Parkinson, Fiona E" sort="Parkinson, Fiona E" uniqKey="Parkinson F" first="Fiona E." last="Parkinson">Fiona E. Parkinson</name><name sortKey="Sitar, Daniel S" sort="Sitar, Daniel S" uniqKey="Sitar D" first="Daniel S." last="Sitar">Daniel S. Sitar</name><name sortKey="Sitar, Daniel S" sort="Sitar, Daniel S" uniqKey="Sitar D" first="Daniel S." last="Sitar">Daniel S. Sitar</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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