作者
Anindya Bhattacharya, Qi Wang, Hong Ao, James R Shoblock, Brian Lord, Leah Aluisio, Ian Fraser, Diane Nepomuceno, Robert A Neff, Natalie Welty, Timothy W Lovenberg, Pascal Bonaventure, Alan D Wickenden, Michael A Letavic
发表日期
2013/10
期刊
British journal of pharmacology
卷号
170
期号
3
页码范围
624-640
简介
Background and Purpose
An increasing body of evidence suggests that the purinergic receptor P2X, ligand‐gated ion channel, 7 (P2X7) in the CNS may play a key role in neuropsychiatry, neurodegeneration and chronic pain. In this study, we characterized JNJ‐47965567, a centrally permeable, high‐affinity, selective P2X7 antagonist.
Experimental Approach
We have used a combination of in vitro assays (calcium flux, radioligand binding, electrophysiology, IL‐1β release) in both recombinant and native systems. Target engagement of JNJ‐47965567 was demonstrated by ex vivo receptor binding autoradiography and in vivo blockade of Bz‐ATP induced IL‐1β release in the rat brain. Finally, the efficacy of JNJ‐47965567 was tested in standard models of depression, mania and neuropathic pain.
Key Results
JNJ‐47965567 is potent high affinity (pKi 7.9 ± 0.07), selective human P2X7 antagonist, with no …
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A Bhattacharya, Q Wang, H Ao, JR Shoblock, B Lord… - British journal of pharmacology, 2013