title: Ability of nitrobenzylthioinosine to cross the blood-brain barrier in rats.
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.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: C M
authors.initials: CM
authors.lastname: Anderson
authors.forename: D S
authors.initials: DS
authors.lastname: Sitar
authors.forename: F E
authors.initials: FE
authors.lastname: Parkinson
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000493:pharmacokinetics; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D013873:Thionucleotides; D013868:Thioinosine; D013395:Sucrose; C028318:nitrobenzylthioinosine 5'-monophosphate; C001789:4-nitrobenzylthioinosine