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 (original) (raw)

Harvey, Alan L., Young, Louise C., Kornisiuk, Edgar, Snitcofsky, Marina, Colettis, Natalia, Blanco, Carlos, Jerusalinsky, Diana, Jamieson, Andrew G. ORCID: https://orcid.org/0000-0003-1726-7353, Hartley, Richard C. ORCID: https://orcid.org/0000-0003-1033-5405 and Stone, Trevor W. ORCID: https://orcid.org/0000-0002-5532-0031(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.

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