001031972 001__ 1031972
001031972 005__ 20250203133213.0
001031972 0247_ $$2doi$$a10.1021/jacs.4c08446
001031972 0247_ $$2ISSN$$a0002-7863
001031972 0247_ $$2ISSN$$a1520-5126
001031972 0247_ $$2ISSN$$a1943-2984
001031972 0247_ $$2datacite_doi$$a10.34734/FZJ-2024-05896
001031972 0247_ $$2pmid$$a39383450
001031972 0247_ $$2WOS$$aWOS:001335501100001
001031972 037__ $$aFZJ-2024-05896
001031972 082__ $$a540
001031972 1001_ $$0P:(DE-HGF)0$$aMaleeva, Galyna$$b0
001031972 245__ $$aLight-Activated Agonist-Potentiator of GABA A Receptors for Reversible Neuroinhibition in Wildtype Mice
001031972 260__ $$aWashington, DC$$bACS Publications$$c2024
001031972 3367_ $$2DRIVER$$aarticle
001031972 3367_ $$2DataCite$$aOutput Types/Journal article
001031972 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1738060575_6609
001031972 3367_ $$2BibTeX$$aARTICLE
001031972 3367_ $$2ORCID$$aJOURNAL_ARTICLE
001031972 3367_ $$00$$2EndNote$$aJournal Article
001031972 520__ $$aGamma aminobutyric acid type A receptors (GABAARs) play a key role in the mammalian central nervous system (CNS) as drivers of neuroinhibitory circuits, which are commonly targeted for therapeutic purposes with potentiator drugs. However, due to their widespread expression and strong inhibitory action, systemic pharmaceutical potentiation of GABAARs inevitably causes adverse effects regardless of the drug selectivity. Therefore, therapeutic guidelines must often limit or exclude clinically available GABAAR potentiators, despite their high efficacy, good biodistribution, and favorable molecular properties. One solution to this problem is to use drugs with light-dependent activity (photopharmacology) in combination with on-demand, localized illumination. However, a suitable light-activated potentiator of GABAARs has been elusive so far for use in wildtype mammals. We have met this need by developing azocarnil, a diffusible GABAergic agonist-potentiator based on the anxiolytic drug abecarnil that is inactive in the dark and activated by visible violet light. Azocarnil can be rapidly deactivated with green light and by thermal relaxation in the dark. We demonstrate that it selectively inhibits neuronal currents in hippocampal neurons in vitro and in the dorsal horns of the spinal cord of mice, decreasing the mechanical sensitivity as a function of illumination without displaying systemic adverse effects. Azocarnil expands the in vivo photopharmacological toolkit with a novel chemical scaffold and achieves a milestone toward future phototherapeutic applications to safely treat muscle spasms, pain, anxiety, sleep disorders, and epilepsy.
001031972 536__ $$0G:(DE-HGF)POF4-5241$$a5241 - Molecular Information Processing in Cellular Systems (POF4-524)$$cPOF4-524$$fPOF IV$$x0
001031972 536__ $$0G:(DE-HGF)POF4-5251$$a5251 - Multilevel Brain Organization and Variability (POF4-525)$$cPOF4-525$$fPOF IV$$x1
001031972 536__ $$0G:(DE-HGF)POF4-5252$$a5252 - Brain Dysfunction and Plasticity (POF4-525)$$cPOF4-525$$fPOF IV$$x2
001031972 536__ $$0G:(GEPRIS)291198853$$aDFG project G:(GEPRIS)291198853 - FOR 2518: Funktionale Dynamik von Ionenkanälen und Transportern - DynIon - (291198853)$$c291198853$$x3
001031972 536__ $$0G:(GEPRIS)329460521$$aDFG project G:(GEPRIS)329460521 - Protonentransfer und Substraterkennung in SLC17-Transportern (329460521)$$c329460521$$x4
001031972 588__ $$aDataset connected to CrossRef, Journals: juser.fz-juelich.de
001031972 7001_ $$00000-0002-8670-9031$$aNin-Hill, Alba$$b1
001031972 7001_ $$0P:(DE-HGF)0$$aWirth, Ulrike$$b2
001031972 7001_ $$0P:(DE-HGF)0$$aRustler, Karin$$b3
001031972 7001_ $$0P:(DE-HGF)0$$aRanucci, Matteo$$b4
001031972 7001_ $$0P:(DE-HGF)0$$aOpar, Ekin$$b5
001031972 7001_ $$00000-0003-1477-5010$$aRovira, Carme$$b6
001031972 7001_ $$0P:(DE-HGF)0$$aBregestovski, Piotr$$b7
001031972 7001_ $$0P:(DE-HGF)0$$aZeilhofer, Hanns Ulrich$$b8
001031972 7001_ $$00000-0002-6131-4850$$aKönig, Burkhard$$b9
001031972 7001_ $$0P:(DE-Juel1)169976$$aAlfonso-Prieto, Mercedes$$b10$$eCorresponding author$$ufzj
001031972 7001_ $$00000-0002-7268-5577$$aGorostiza, Pau$$b11$$eCorresponding author
001031972 773__ $$0PERI:(DE-600)1472210-0$$a10.1021/jacs.4c08446$$gp. jacs.4c08446$$n42$$p28822-28831$$tJournal of the American Chemical Society$$v146$$x0002-7863$$y2024
001031972 8564_ $$uhttps://juser.fz-juelich.de/record/1031972/files/Invoice_202400144_Julich.pdf
001031972 8564_ $$uhttps://juser.fz-juelich.de/record/1031972/files/maleeva-et-al-2024-light-activated-agonist-potentiator-of-gabaa-receptors-for-reversible-neuroinhibition-in-wildtype.pdf$$yOpenAccess
001031972 8767_ $$8202400144$$92024-10-29$$a1200208407$$d2024-11-19$$ePayment fee$$jZahlung erfolgt$$zInstitut beteiligt liegt an Kostenübernahme , Zahlung an Barcelona
001031972 909CO $$ooai:juser.fz-juelich.de:1031972$$pdnbdelivery$$popenCost$$pVDB$$pdriver$$pOpenAPC$$popen_access$$popenaire
001031972 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)169976$$aForschungszentrum Jülich$$b10$$kFZJ
001031972 9131_ $$0G:(DE-HGF)POF4-524$$1G:(DE-HGF)POF4-520$$2G:(DE-HGF)POF4-500$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF4-5241$$aDE-HGF$$bKey Technologies$$lNatural, Artificial and Cognitive Information Processing$$vMolecular and Cellular Information Processing$$x0
001031972 9131_ $$0G:(DE-HGF)POF4-525$$1G:(DE-HGF)POF4-520$$2G:(DE-HGF)POF4-500$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF4-5251$$aDE-HGF$$bKey Technologies$$lNatural, Artificial and Cognitive Information Processing$$vDecoding Brain Organization and Dysfunction$$x1
001031972 9131_ $$0G:(DE-HGF)POF4-525$$1G:(DE-HGF)POF4-520$$2G:(DE-HGF)POF4-500$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF4-5252$$aDE-HGF$$bKey Technologies$$lNatural, Artificial and Cognitive Information Processing$$vDecoding Brain Organization and Dysfunction$$x2
001031972 9141_ $$y2024
001031972 915pc $$0PC:(DE-HGF)0000$$2APC$$aAPC keys set
001031972 915pc $$0PC:(DE-HGF)0001$$2APC$$aLocal Funding
001031972 915pc $$0PC:(DE-HGF)0002$$2APC$$aDFG OA Publikationskosten
001031972 915pc $$0PC:(DE-HGF)0122$$2APC$$aHelmholtz: American Chemical Society 01/01/2023
001031972 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2023-10-21
001031972 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2023-10-21
001031972 915__ $$0LIC:(DE-HGF)CCBYNCND4$$2HGFVOC$$aCreative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0
001031972 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2023-10-21
001031972 915__ $$0StatID:(DE-HGF)1210$$2StatID$$aDBCoverage$$bIndex Chemicus$$d2023-10-21
001031972 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
001031972 915__ $$0StatID:(DE-HGF)1200$$2StatID$$aDBCoverage$$bChemical Reactions$$d2023-10-21
001031972 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz$$d2024-12-13$$wger
001031972 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bJ AM CHEM SOC : 2022$$d2024-12-13
001031972 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2024-12-13
001031972 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2024-12-13
001031972 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2024-12-13
001031972 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2024-12-13
001031972 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2024-12-13
001031972 915__ $$0StatID:(DE-HGF)1150$$2StatID$$aDBCoverage$$bCurrent Contents - Physical, Chemical and Earth Sciences$$d2024-12-13
001031972 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2024-12-13
001031972 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2024-12-13
001031972 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2024-12-13
001031972 915__ $$0StatID:(DE-HGF)9915$$2StatID$$aIF >= 15$$bJ AM CHEM SOC : 2022$$d2024-12-13
001031972 920__ $$lyes
001031972 9201_ $$0I:(DE-Juel1)INM-9-20140121$$kINM-9$$lComputational Biomedicine$$x0
001031972 9201_ $$0I:(DE-Juel1)IAS-5-20120330$$kIAS-5$$lComputational Biomedicine$$x1
001031972 980__ $$ajournal
001031972 980__ $$aVDB
001031972 980__ $$aUNRESTRICTED
001031972 980__ $$aI:(DE-Juel1)INM-9-20140121
001031972 980__ $$aI:(DE-Juel1)IAS-5-20120330
001031972 980__ $$aAPC
001031972 9801_ $$aAPC
001031972 9801_ $$aFullTexts