Artículo
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.; 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.
Fecha de publicación:
10/2012
Editorial:
Elsevier Science
Revista:
Behavioural Brain Research
ISSN:
0166-4328
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
A1 Receptors
,
Adenosine
,
Hippocampus
,
Non-Xanthine Antagonists
,
Purine Receptors
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Articulos(IBCN)
Articulos de INST.DE BIOLO.CEL.Y NEURCS."PROF.E.DE ROBERTIS"
Articulos de INST.DE BIOLO.CEL.Y NEURCS."PROF.E.DE ROBERTIS"
Citación
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
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