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Article: Acetoxymethoxycarbonyl nitroxides as electron paramagnetic resonance proimaging agents to measure O2 levels in mouse brain: A pharmacokinetic and pharmacodynamic study

TitleAcetoxymethoxycarbonyl nitroxides as electron paramagnetic resonance proimaging agents to measure O2 levels in mouse brain: A pharmacokinetic and pharmacodynamic study
Authors
Issue Date2006
PublisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://jpet.aspetjournals.org
Citation
Journal Of Pharmacology And Experimental Therapeutics, 2006, v. 318 n. 3, p. 1187-1193 How to Cite?
AbstractMeasurement of O2 concentration and distribution in brain is essential to understanding the pathophysiology of stroke. Low-frequency electron paramagnetic resonance (EPR) spectroscopy with a paramagnetic probe is an attractive imaging modality that can potentially map O2 concentration in the brain. In a previous study, we demonstrated that, after intraperitoneal administration of 3-acetoxymethoxycarbonyl-2,2,5,5-tetramethyl-1- pyrrolidinyloxyl (1) to mice, this nitroxide crossed the blood-brain barrier into brain tissue where, after hydrolysis, 3-carboxy-2,2,5,5-tetramethyl-1- pyrrolidinyloxyl (2) was liberated and entrapped. This pilot study suggested that nitroxide 1 is a proimaging agent that can deliver nitroxide 2 to brain tissue, where O2 levels can be estimated. In the present study, we conducted a series of pharmacokinetic and pharmacodynamic experiments designed to assess the uptake of structurally disparate nitroxides into brain tissue and retention, after hydrolysis, of the anions of the corresponding nitroxide acids. From these findings, nitroxide 1 and trans-3,4-di(acetoxymethoxycarbonyl)-2,2, 5,5-tetramethyl-1-pyrrolidinyloxyl (5) meet the requirement as EPR proimaging agents for mapping O2 distribution in the brain following stroke. Copyright © 2006 by The American Society for Pharmacology and Experimental Therapeutics.
Persistent Identifierhttp://hdl.handle.net/10722/89651
ISSN
2014 Impact Factor: 3.972
2014 SCImago Journal Rankings: 1.514
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMiyake, Men_HK
dc.contributor.authorShen, Jen_HK
dc.contributor.authorLiu, Sen_HK
dc.contributor.authorShi, Hen_HK
dc.contributor.authorLiu, Wen_HK
dc.contributor.authorYuan, Zen_HK
dc.contributor.authorPritchard, Aen_HK
dc.contributor.authorKao, JPYen_HK
dc.contributor.authorKe, JLen_HK
dc.contributor.authorRosen, GMen_HK
dc.date.accessioned2010-09-06T09:59:55Z-
dc.date.available2010-09-06T09:59:55Z-
dc.date.issued2006en_HK
dc.identifier.citationJournal Of Pharmacology And Experimental Therapeutics, 2006, v. 318 n. 3, p. 1187-1193en_HK
dc.identifier.issn0022-3565en_HK
dc.identifier.urihttp://hdl.handle.net/10722/89651-
dc.description.abstractMeasurement of O2 concentration and distribution in brain is essential to understanding the pathophysiology of stroke. Low-frequency electron paramagnetic resonance (EPR) spectroscopy with a paramagnetic probe is an attractive imaging modality that can potentially map O2 concentration in the brain. In a previous study, we demonstrated that, after intraperitoneal administration of 3-acetoxymethoxycarbonyl-2,2,5,5-tetramethyl-1- pyrrolidinyloxyl (1) to mice, this nitroxide crossed the blood-brain barrier into brain tissue where, after hydrolysis, 3-carboxy-2,2,5,5-tetramethyl-1- pyrrolidinyloxyl (2) was liberated and entrapped. This pilot study suggested that nitroxide 1 is a proimaging agent that can deliver nitroxide 2 to brain tissue, where O2 levels can be estimated. In the present study, we conducted a series of pharmacokinetic and pharmacodynamic experiments designed to assess the uptake of structurally disparate nitroxides into brain tissue and retention, after hydrolysis, of the anions of the corresponding nitroxide acids. From these findings, nitroxide 1 and trans-3,4-di(acetoxymethoxycarbonyl)-2,2, 5,5-tetramethyl-1-pyrrolidinyloxyl (5) meet the requirement as EPR proimaging agents for mapping O2 distribution in the brain following stroke. Copyright © 2006 by The American Society for Pharmacology and Experimental Therapeutics.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://jpet.aspetjournals.orgen_HK
dc.relation.ispartofJournal of Pharmacology and Experimental Therapeuticsen_HK
dc.titleAcetoxymethoxycarbonyl nitroxides as electron paramagnetic resonance proimaging agents to measure O2 levels in mouse brain: A pharmacokinetic and pharmacodynamic studyen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-3565&volume=318&issue=3&spage=1187&epage=1193&date=2006&atitle=Acetoxymethoxycarbonyl+nitroxides+as+electron+paramagnetic+resonance+proimaging+agents+to+measure+O2+levels+in+mouse+brain:+a+pharmacokinetic+and+pharmacodynamic+study.en_HK
dc.identifier.emailShen, J: shenjg@hku.hken_HK
dc.identifier.authorityShen, J=rp00487en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1124/jpet.106.106245en_HK
dc.identifier.pmid16757536-
dc.identifier.scopuseid_2-s2.0-33747599876en_HK
dc.identifier.hkuros134648en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33747599876&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume318en_HK
dc.identifier.issue3en_HK
dc.identifier.spage1187en_HK
dc.identifier.epage1193en_HK
dc.identifier.isiWOS:000239878900030-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridMiyake, M=7201843244en_HK
dc.identifier.scopusauthoridShen, J=7404929947en_HK
dc.identifier.scopusauthoridLiu, S=36094288000en_HK
dc.identifier.scopusauthoridShi, H=7402623561en_HK
dc.identifier.scopusauthoridLiu, W=7407343965en_HK
dc.identifier.scopusauthoridYuan, Z=7401477205en_HK
dc.identifier.scopusauthoridPritchard, A=14008681800en_HK
dc.identifier.scopusauthoridKao, JPY=7201375605en_HK
dc.identifier.scopusauthoridKe, JL=7102915373en_HK
dc.identifier.scopusauthoridRosen, GM=35497253700en_HK

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