jnj-47965567 has been researched along with Neuralgia* in 1 studies
1 other study(ies) available for jnj-47965567 and Neuralgia
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Pharmacological characterization of a novel centrally permeable P2X7 receptor antagonist: JNJ-47965567.
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.. 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.. JNJ-47965567 is potent high affinity (pKi 7.9 ± 0.07), selective human P2X7 antagonist, with no significant observed speciation. In native systems, the potency of the compound to attenuate IL-1β release was 6.7 ± 0.07 (human blood), 7.5 ± 0.07 (human monocytes) and 7.1 ± 0.1 (rat microglia). JNJ-47965567 exhibited target engagement in rat brain, with a brain EC50 of 78 ± 19 ng·mL(-1) (P2X7 receptor autoradiography) and functional block of Bz-ATP induced IL-1β release. JNJ-47965567 (30 mg·kg(-1) ) attenuated amphetamine-induced hyperactivity and exhibited modest, yet significant efficacy in the rat model of neuropathic pain. No efficacy was observed in forced swim test.. JNJ-47965567 is centrally permeable, high affinity P2X7 antagonist that can be used to probe the role of central P2X7 in rodent models of CNS pathophysiology. Topics: Adenosine Triphosphate; Analgesics; Animals; Antidepressive Agents; Antimanic Agents; Behavior, Animal; Binding, Competitive; Bipolar Disorder; Blood-Brain Barrier; Brain; Calcium Signaling; Capillary Permeability; Cell Line; Depression; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Humans; Interleukin-1beta; Macaca; Male; Mice; Mice, Inbred C57BL; Neuralgia; Niacinamide; Piperazines; Protein Binding; Purinergic P2X Receptor Antagonists; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P2X7; Time Factors; Transfection | 2013 |