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dc.contributor.authorShaukat Husain, S.en_US
dc.contributor.authorNirthanan, Selvanayagamen_US
dc.contributor.authorRuesch, Dirken_US
dc.contributor.authorSolt, Kenen_US
dc.contributor.authorCheng, Qien_US
dc.contributor.authorLi, Guo-Dongen_US
dc.contributor.authorArevalo, Enriqueen_US
dc.contributor.authorW. Olsen, Richarden_US
dc.contributor.authorE. Raines, Douglasen_US
dc.contributor.authorA. Forman, Stuarten_US
dc.contributor.authorB. Cohen, Jonathanen_US
dc.contributor.authorW. Miller, Keithen_US
dc.date.accessioned2017-05-03T15:28:59Z
dc.date.available2017-05-03T15:28:59Z
dc.date.issued2006en_US
dc.date.modified2009-09-28T06:52:24Z
dc.identifier.issn00222623en_US
dc.identifier.doi10.1021/jm051207ben_AU
dc.identifier.urihttp://hdl.handle.net/10072/25850
dc.description.abstractTo locate the binding sites of general anesthetics on ligand-gated ion channels, two derivatives of the intravenous general anesthetic etomidate (2-ethyl 1-(phenylethyl)-1H-imidazole-5-carboxylate), in which the 2-ethyl group has been replaced by photoactivable groups based on either aryl diazirine or benzophenone chemistry, have been synthesized and characterized pharmacologically. TDBzl-etomidate (4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate) and BzBzl-etomidate (4-benzoylbenzyl-1-(1-phenylethyl)-1H-imidazole-5-carboxylate are both potent general anesthetics with half-effective anesthetic concentrations of 700 and 220 nM, respectively. Both agents resembled etomidate in enhancing currents elicited by low concentrations of GABA on heterologously expressed GABAA receptors and in shifting the GABA concentration-response curve to lower concentrations. They also allosterically enhanced the binding of flunitrazepam to mammalian brain GABAA receptors. Both agents were also effective and selective photolabels, photoincorporating into some, but not all, subunits of the Torpedo nicotinic acetylcholine receptor to a degree that was allosterically regulated by an agonist or a noncompetitive inhibitor. Thus, they have the necessary pharmacological and photochemical properties to be useful in identifying the site of etomidate-induced anesthesia.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_AU
dc.languageEnglishen_US
dc.language.isoen_AU
dc.publisherAmerican Chemical Societyen_US
dc.publisher.placeWashington, DCen_US
dc.relation.ispartofstudentpublicationNen_AU
dc.relation.ispartofpagefrom4818en_US
dc.relation.ispartofpageto4825en_US
dc.relation.ispartofissue16en_US
dc.relation.ispartofjournalJournal of Medicinal Chemistryen_US
dc.relation.ispartofvolume49en_US
dc.rights.retentionYen_AU
dc.subject.fieldofresearchCentral Nervous Systemen_US
dc.subject.fieldofresearchPharmaceutical Sciencesen_US
dc.subject.fieldofresearchcode110903en_US
dc.subject.fieldofresearchcode111504en_US
dc.titleSynthesis of Trifluoromethylaryl Diazirine and Benzophenone Derivatives of Etomidate that Are Potent General Anesthetics and Effective Photolabels for Probing Sites on Ligand-Gated Ion Channelsen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.date.issued2006
gro.hasfulltextNo Full Text


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