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

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• 作者：Alan L. Harvey ; Louise C. Young ; Edgar Kornisiuk ; Marina Snitcofsky ; Natalia Colettis ; Carlos Blanco ; Diana Jerusalinsky ; Andrew G. Jamieson ; Richard C. Hartley ; Trevor W. Stone
• 关键词：AJ23 ; 7-methyl-1-phenyl-1 ; 8-dihydropyrazolo-(3 ; 4d)(1 ; 2 ; 4)triazolo(1 ; 5a)pyrimidin-4-one ; ACSF ; artificial cerebrospinal fluid ; CHO ; Chinese Hamster Ovary ; DMSO ; d6 &ndash ; dimethylsulphoxide ; DPCPX ; 1 ; 3-dipropyl-8-cyclopentylxanthine ; HEK ; Human Embryonic
• 刊名：Behavioural Brain Research
• 出版年：2012
• 出版时间：1 October, 2012
• 年：2012
• 卷：234
• 期：2
• 页码：184-191
• 全文大小：417 K

文摘

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 A_2A 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.