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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
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TitleAcetoxymethoxycarbonyl nitroxides as electron paramagnetic resonance proimaging agents to measure O2 levels in mouse brain: A pharmacokinetic and pharmacodynamic study
 
AuthorsMiyake, M4
Shen, J4 3
Liu, S4
Shi, H4
Liu, W4
Yuan, Z4
Pritchard, A4
Kao, JPY5 1
Ke, JL4
Rosen, GM5 2
 
Issue Date2006
 
PublisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://jpet.aspetjournals.org
 
CitationJournal Of Pharmacology And Experimental Therapeutics, 2006, v. 318 n. 3, p. 1187-1193 [How to Cite?]
DOI: http://dx.doi.org/10.1124/jpet.106.106245
 
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.
 
ISSN0022-3565
2013 Impact Factor: 3.855
 
DOIhttp://dx.doi.org/10.1124/jpet.106.106245
 
ISI Accession Number IDWOS:000239878900030
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorMiyake, M
 
dc.contributor.authorShen, J
 
dc.contributor.authorLiu, S
 
dc.contributor.authorShi, H
 
dc.contributor.authorLiu, W
 
dc.contributor.authorYuan, Z
 
dc.contributor.authorPritchard, A
 
dc.contributor.authorKao, JPY
 
dc.contributor.authorKe, JL
 
dc.contributor.authorRosen, GM
 
dc.date.accessioned2010-09-06T09:59:55Z
 
dc.date.available2010-09-06T09:59:55Z
 
dc.date.issued2006
 
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.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of Pharmacology And Experimental Therapeutics, 2006, v. 318 n. 3, p. 1187-1193 [How to Cite?]
DOI: http://dx.doi.org/10.1124/jpet.106.106245
 
dc.identifier.doihttp://dx.doi.org/10.1124/jpet.106.106245
 
dc.identifier.epage1193
 
dc.identifier.hkuros134648
 
dc.identifier.isiWOS:000239878900030
 
dc.identifier.issn0022-3565
2013 Impact Factor: 3.855
 
dc.identifier.issue3
 
dc.identifier.openurl
 
dc.identifier.pmid16757536
 
dc.identifier.scopuseid_2-s2.0-33747599876
 
dc.identifier.spage1187
 
dc.identifier.urihttp://hdl.handle.net/10722/89651
 
dc.identifier.volume318
 
dc.languageeng
 
dc.publisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://jpet.aspetjournals.org
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Pharmacology and Experimental Therapeutics
 
dc.relation.referencesReferences in Scopus
 
dc.titleAcetoxymethoxycarbonyl nitroxides as electron paramagnetic resonance proimaging agents to measure O2 levels in mouse brain: A pharmacokinetic and pharmacodynamic study
 
dc.typeArticle
 
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Author Affiliations
  1. University of Maryland School of Medicine
  2. University of Maryland School of Pharmacy
  3. The University of Hong Kong
  4. University of New Mexico
  5. UMBI