Pharmacological characterization of a novel centrally permeable P2X7 receptor antagonist: JNJ-47965567.

ABSTRACT:

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.<

SUBMITTER: Bhattacharya A 

PROVIDER: S-EPMC3792000 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature