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, A. L., Young, L. C., Kornisiuk, E., Snitcofsky, M., Colettis, N., Blanco, C., Jerusalinsky, D., Jamieson, A. G. , Hartley, R. C. and Stone, T. W. (2012) 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. Behavioural Brain Research, 234(2), pp. 184-191. (doi:10.1016/j.bbr.2012.06.023)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hartley, Professor Richard and Stone, Professor Trevor and Jamieson, Dr Andrew
Authors: Harvey, A. L., Young, L. C., Kornisiuk, E., Snitcofsky, M., Colettis, N., Blanco, C., Jerusalinsky, D., Jamieson, A. G., Hartley, R. C., and Stone, T. W.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
College of Science and Engineering > School of Chemistry
Journal Name:Behavioural Brain Research
Publisher:Elsevier
ISSN:0166-4328
ISSN (Online):1872-7549
Published Online:27 June 2012

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