A novel dihydro-pyrazolo(3,4d)(1,2,4)triazolo(1,5a)pyrimidin-4-one (AJ23) is an antagonist at adenosine A1 receptors and enhances consolidation of step-down avoidance

Autores
Harvey, Alan L.; Young, Louise C.; Kornisiuk, Edgar Ernesto; Snitcofsky, Marina; Colettis, Natalia Claudia; Blanco, Carlos; Jerusalinsky, Diana Alicia; Jamieson, Andrew G.; Hartley, Richard C.; Stone, Trevor W.
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Adenosine A1 receptor antagonists are of potential value in the treatment of cognitive dysfunction. We have developed compound AJ23 (7-methyl-1-phenyl-1,8-dihydro-pyrazolo-(3,4d)(1,2,4)-triazolo(1,5a)-pyrimidin-4-one) as a novel, non-xanthine based antagonist at A1 receptors. It has micromolar affinity at human A1 receptors with a 45-fold selectivity for A1 over A2A receptors and little affinity for many other receptors and transporters tested in a screening panel. AJ23 blocks A1 receptors in the rat hippocampus, increasing the baseline size of excitatory post-synaptic potentials and blocking the inhibitory effects of adenosine. When administered directly into the rodent hippocampus this compound improves consolidation in a step-down avoidance learning task. The results suggest that AJ23 or derivatives may represent possible leads for further chemical development towards a chemically novel group of antagonists at A1 receptors with potential value as cognitive enhancers. © 2012.
Fil: Harvey, Alan L.. University of Strathclyde; Reino Unido
Fil: Young, Louise C.. University of Strathclyde; Reino Unido
Fil: Kornisiuk, Edgar Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Snitcofsky, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Colettis, Natalia Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Blanco, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Jerusalinsky, Diana Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Universidad de Buenos Aires. Ciclo Básico Común; Argentina
Fil: Jamieson, Andrew G.. University of Glasgow; Reino Unido
Fil: Hartley, Richard C.. University of Glasgow; Reino Unido
Fil: Stone, Trevor W.. University of Glasgow; Reino Unido
Materia
A1 Receptors
Adenosine
Hippocampus
Non-Xanthine Antagonists
Purine Receptors
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/67435
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/67435
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A novel dihydro-pyrazolo(3,4d)(1,2,4)triazolo(1,5a)pyrimidin-4-one (AJ23) is an antagonist at adenosine A1 receptors and enhances consolidation of step-down avoidanceHarvey, Alan L.Young, Louise C.Kornisiuk, Edgar ErnestoSnitcofsky, MarinaColettis, Natalia ClaudiaBlanco, CarlosJerusalinsky, Diana AliciaJamieson, Andrew G.Hartley, Richard C.Stone, Trevor W.A1 ReceptorsAdenosineHippocampusNon-Xanthine AntagonistsPurine Receptorshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Adenosine A1 receptor antagonists are of potential value in the treatment of cognitive dysfunction. We have developed compound AJ23 (7-methyl-1-phenyl-1,8-dihydro-pyrazolo-(3,4d)(1,2,4)-triazolo(1,5a)-pyrimidin-4-one) as a novel, non-xanthine based antagonist at A1 receptors. It has micromolar affinity at human A1 receptors with a 45-fold selectivity for A1 over A2A receptors and little affinity for many other receptors and transporters tested in a screening panel. AJ23 blocks A1 receptors in the rat hippocampus, increasing the baseline size of excitatory post-synaptic potentials and blocking the inhibitory effects of adenosine. When administered directly into the rodent hippocampus this compound improves consolidation in a step-down avoidance learning task. The results suggest that AJ23 or derivatives may represent possible leads for further chemical development towards a chemically novel group of antagonists at A1 receptors with potential value as cognitive enhancers. © 2012.Fil: Harvey, Alan L.. University of Strathclyde; Reino UnidoFil: Young, Louise C.. University of Strathclyde; Reino UnidoFil: Kornisiuk, Edgar Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Snitcofsky, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Colettis, Natalia Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Blanco, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Jerusalinsky, Diana Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Universidad de Buenos Aires. Ciclo Básico Común; ArgentinaFil: Jamieson, Andrew G.. University of Glasgow; Reino UnidoFil: Hartley, Richard C.. University of Glasgow; Reino UnidoFil: Stone, Trevor W.. University of Glasgow; Reino UnidoElsevier Science2012-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/67435Harvey, Alan L.; Young, Louise C.; Kornisiuk, Edgar Ernesto; Snitcofsky, Marina; Colettis, Natalia Claudia; et al.; A novel dihydro-pyrazolo(3,4d)(1,2,4)triazolo(1,5a)pyrimidin-4-one (AJ23) is an antagonist at adenosine A1 receptors and enhances consolidation of step-down avoidance; Elsevier Science; Behavioural Brain Research; 234; 2; 10-2012; 184-1910166-4328CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbr.2012.06.023info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0166432812004366info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-05-06T16:35:30Zoai:ri.conicet.gov.ar:11336/67435instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-05-06 16:35:31.155CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A novel dihydro-pyrazolo(3,4d)(1,2,4)triazolo(1,5a)pyrimidin-4-one (AJ23) is an antagonist at adenosine A1 receptors and enhances consolidation of step-down avoidance
title A novel dihydro-pyrazolo(3,4d)(1,2,4)triazolo(1,5a)pyrimidin-4-one (AJ23) is an antagonist at adenosine A1 receptors and enhances consolidation of step-down avoidance
spellingShingle A novel dihydro-pyrazolo(3,4d)(1,2,4)triazolo(1,5a)pyrimidin-4-one (AJ23) is an antagonist at adenosine A1 receptors and enhances consolidation of step-down avoidance
Harvey, Alan L.
A1 Receptors
Adenosine
Hippocampus
Non-Xanthine Antagonists
Purine Receptors
title_short A novel dihydro-pyrazolo(3,4d)(1,2,4)triazolo(1,5a)pyrimidin-4-one (AJ23) is an antagonist at adenosine A1 receptors and enhances consolidation of step-down avoidance
title_full A novel dihydro-pyrazolo(3,4d)(1,2,4)triazolo(1,5a)pyrimidin-4-one (AJ23) is an antagonist at adenosine A1 receptors and enhances consolidation of step-down avoidance
title_fullStr A novel dihydro-pyrazolo(3,4d)(1,2,4)triazolo(1,5a)pyrimidin-4-one (AJ23) is an antagonist at adenosine A1 receptors and enhances consolidation of step-down avoidance
title_full_unstemmed A novel dihydro-pyrazolo(3,4d)(1,2,4)triazolo(1,5a)pyrimidin-4-one (AJ23) is an antagonist at adenosine A1 receptors and enhances consolidation of step-down avoidance
title_sort A novel dihydro-pyrazolo(3,4d)(1,2,4)triazolo(1,5a)pyrimidin-4-one (AJ23) is an antagonist at adenosine A1 receptors and enhances consolidation of step-down avoidance
dc.creator.none.fl_str_mv Harvey, Alan L.
Young, Louise C.
Kornisiuk, Edgar Ernesto
Snitcofsky, Marina
Colettis, Natalia Claudia
Blanco, Carlos
Jerusalinsky, Diana Alicia
Jamieson, Andrew G.
Hartley, Richard C.
Stone, Trevor W.
author Harvey, Alan L.
author_facet Harvey, Alan L.
Young, Louise C.
Kornisiuk, Edgar Ernesto
Snitcofsky, Marina
Colettis, Natalia Claudia
Blanco, Carlos
Jerusalinsky, Diana Alicia
Jamieson, Andrew G.
Hartley, Richard C.
Stone, Trevor W.
author_role author
author2 Young, Louise C.
Kornisiuk, Edgar Ernesto
Snitcofsky, Marina
Colettis, Natalia Claudia
Blanco, Carlos
Jerusalinsky, Diana Alicia
Jamieson, Andrew G.
Hartley, Richard C.
Stone, Trevor W.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv A1 Receptors
Adenosine
Hippocampus
Non-Xanthine Antagonists
Purine Receptors
topic A1 Receptors
Adenosine
Hippocampus
Non-Xanthine Antagonists
Purine Receptors
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Adenosine A1 receptor antagonists are of potential value in the treatment of cognitive dysfunction. We have developed compound AJ23 (7-methyl-1-phenyl-1,8-dihydro-pyrazolo-(3,4d)(1,2,4)-triazolo(1,5a)-pyrimidin-4-one) as a novel, non-xanthine based antagonist at A1 receptors. It has micromolar affinity at human A1 receptors with a 45-fold selectivity for A1 over A2A receptors and little affinity for many other receptors and transporters tested in a screening panel. AJ23 blocks A1 receptors in the rat hippocampus, increasing the baseline size of excitatory post-synaptic potentials and blocking the inhibitory effects of adenosine. When administered directly into the rodent hippocampus this compound improves consolidation in a step-down avoidance learning task. The results suggest that AJ23 or derivatives may represent possible leads for further chemical development towards a chemically novel group of antagonists at A1 receptors with potential value as cognitive enhancers. © 2012.
Fil: Harvey, Alan L.. University of Strathclyde; Reino Unido
Fil: Young, Louise C.. University of Strathclyde; Reino Unido
Fil: Kornisiuk, Edgar Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Snitcofsky, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Colettis, Natalia Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Blanco, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Jerusalinsky, Diana Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Universidad de Buenos Aires. Ciclo Básico Común; Argentina
Fil: Jamieson, Andrew G.. University of Glasgow; Reino Unido
Fil: Hartley, Richard C.. University of Glasgow; Reino Unido
Fil: Stone, Trevor W.. University of Glasgow; Reino Unido
description Adenosine A1 receptor antagonists are of potential value in the treatment of cognitive dysfunction. We have developed compound AJ23 (7-methyl-1-phenyl-1,8-dihydro-pyrazolo-(3,4d)(1,2,4)-triazolo(1,5a)-pyrimidin-4-one) as a novel, non-xanthine based antagonist at A1 receptors. It has micromolar affinity at human A1 receptors with a 45-fold selectivity for A1 over A2A receptors and little affinity for many other receptors and transporters tested in a screening panel. AJ23 blocks A1 receptors in the rat hippocampus, increasing the baseline size of excitatory post-synaptic potentials and blocking the inhibitory effects of adenosine. When administered directly into the rodent hippocampus this compound improves consolidation in a step-down avoidance learning task. The results suggest that AJ23 or derivatives may represent possible leads for further chemical development towards a chemically novel group of antagonists at A1 receptors with potential value as cognitive enhancers. © 2012.
publishDate 2012
dc.date.none.fl_str_mv 2012-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/67435
Harvey, Alan L.; Young, Louise C.; Kornisiuk, Edgar Ernesto; Snitcofsky, Marina; Colettis, Natalia Claudia; et al.; A novel dihydro-pyrazolo(3,4d)(1,2,4)triazolo(1,5a)pyrimidin-4-one (AJ23) is an antagonist at adenosine A1 receptors and enhances consolidation of step-down avoidance; Elsevier Science; Behavioural Brain Research; 234; 2; 10-2012; 184-191
0166-4328
CONICET Digital
CONICET
url http://hdl.handle.net/11336/67435
identifier_str_mv Harvey, Alan L.; Young, Louise C.; Kornisiuk, Edgar Ernesto; Snitcofsky, Marina; Colettis, Natalia Claudia; et al.; A novel dihydro-pyrazolo(3,4d)(1,2,4)triazolo(1,5a)pyrimidin-4-one (AJ23) is an antagonist at adenosine A1 receptors and enhances consolidation of step-down avoidance; Elsevier Science; Behavioural Brain Research; 234; 2; 10-2012; 184-191
0166-4328
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbr.2012.06.023
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0166432812004366
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.1485815

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