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

作者：Harvey Alan L; Young Louise C; Kornisiuk Edgar; Snitcofsky Marina; Colettis Natalia; Blanco Carlos; Jerusalinsky Diana; Jamieson Andrew G; Hartley Richard C; Stone Trevor W^*

来源：Behavioural Brain Research, 2012, 234(2): 184-191.

DOI：10.1016/j.bbr.2012.06.023

• Adenosine
• A(1) receptors
• Non-xanthine antagonists
• Purine receptors
• Hippocampus

Adenosine A(1) 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 A(1) receptors with a 45-fold selectivity for A(1) over A(2A) receptors and little affinity for many other receptors and transporters tested in a screening panel. AJ23 blocks A(1) 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 A(1) receptors with potential value as cognitive enhancers.

• 出版日期2012-10-1