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

British Journal of Pharmacology

Volumn 170, Issue 3, 2013, Pages 624-640

  Bhattacharya, Anindya ^a   Wang, Qi ^a   Ao, Hong ^a   Shoblock, James R ^a   Lord, Brian ^a   Aluisio, Leah ^a   Fraser, Ian ^a   Nepomuceno, Diane ^a   Neff, Robert A ^a   Welty, Natalie ^a   Lovenberg, Timothy W ^a   Bonaventure, Pascal ^a   Wickenden, Alan D ^a   Letavic, Michael A ^a  

^a JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

autoradiography; depression; interleukin 1 (IL 1 ); mania; microdialysis; neuropathic pain; P2X7; purinergic

Indexed keywords

INTERLEUKIN 1BETA; JNJ 47965567; N [[4 (4 PHENYLPIPERAZIN 1 YL)TETRAHYDRO 2H PYRAN 4 YL]METHYL] 2 (PHENYLTHIO)NICOTINAMIDE; PURINERGIC P2X7 RECEPTOR; PURINERGIC RECEPTOR BLOCKING AGENT; RADIOLIGAND; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; ASTROCYTE; AUTORADIOGRAPHY; BRAIN; CALCIUM TRANSPORT; CONTROLLED STUDY; CYTOKINE RELEASE; DEPRESSION; DRUG EFFICACY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG STRUCTURE; ELECTROPHYSIOLOGY; EX VIVO STUDY; FORCED SWIMMING TEST; HUMAN; HUMAN CELL; IN VITRO STUDY; LIGAND BINDING; MALE; MANIA; MICROGLIA; NEUROPATHIC PAIN; NONHUMAN; PRIORITY JOURNAL; RAT;

AUTORADIOGRAPHY; DEPRESSION; INTERLEUKIN 1Β (IL-1Β); MANIA; MICRODIALYSIS; NEUROPATHIC PAIN; P2X7; PURINERGIC;

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;

EID: 84884546550     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.12314     Document Type: Article

References (63)

1. Abbracchio MP, Burnstock G, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, et al. (2006). International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy. Pharmacol Rev 58: 281-341.
2. Abbracchio MP, Burnstock G, Verkhratsky A, Zimmermann H, (2009). Purinergic signalling in the nervous system: an overview. Trends Neurosci 32: 19-29.
3. Able SL, Fish RL, Bye H, Booth L, Logan YR, Nathaniel C, et al. (2011). Receptor localization, native tissue binding and ex vivo occupancy for centrally penetrant P2X7 antagonists in the rat. Br J Pharmacol 162: 405-414.
4. Alexander SP, Mathie A, Peters JA, (2011). Guide to receptors and channels (GRAC), 5th edn. Br J Pharmacol 164 (Suppl. 1): S1-324.
5. Ando RD, Sperlagh B, (2013). The role of glutamate release mediated by extrasynaptic P2X7 receptors in animal models of neuropathic pain. Brain Res Bull 93: 80-85.
6. Backlund L, Nikamo P, Hukic DS, Ek IR, Traskman-Bendz L, Landen M, et al. (2011). Cognitive manic symptoms associated with the P2RX7 gene in bipolar disorder. Bipolar Disord 13: 500-508.
7. Barden N, Harvey M, Gagne B, Shink E, Tremblay M, Raymond C, et al. (2006). Analysis of single nucleotide polymorphisms in genes in the chromosome 12Q24.31 region points to P2RX7 as a susceptibility gene to bipolar affective disorder. Am J Med Genet B Neuropsychiatr Genet 141B: 374-382.
8. Basso AM, Bratcher NA, Harris RR, Jarvis MF, Decker MW, Rueter LE, (2009). Behavioral profile of P2X7 receptor knockout mice in animal models of depression and anxiety: relevance for neuropsychiatric disorders. Behav Brain Res 198: 83-90.
9. Baxter A, Bent J, Bowers K, Braddock M, Brough S, Fagura M, et al. (2003). Hit-to-Lead studies: the discovery of potent adamantane amide P2X7 receptor antagonists. Bioorg Med Chem Lett 13: 4047-4050.
10. Bennett MR, (2007). Synaptic P2X7 receptor regenerative-loop hypothesis for depression. Aust N Z J Psychiatry 41: 563-571.
11. Bhattacharya A, Neff RA, Wickenden AD, (2011). The physiology, pharmacology and future of P2X7 as an analgesic drug target: hype or promise? Curr Pharm Biotechnol 12: 1698-1706.
12. Boucher AA, Arnold JC, Hunt GE, Spiro A, Spencer J, Brown C, et al. (2011). Resilience and reduced c-Fos expression in P2X7 receptor knockout mice exposed to repeated forced swim test. Neuroscience 189: 170-177.
13. Browne LE, Jiang L-H, North RA, (2010). New structure enlivens interest in P2X receptors. Trends Pharmacol Sci 31: 229-237.
14. Burnstock G, (2008). Purinergic signalling and disorders of the central nervous system. Nat Rev Drug Discov 7: 575-590.
15. Burnstock G, Fredholm BB, Verkhratsky A, (2011a). Adenosine and ATP receptors in the brain. Curr Top Med Chem 11: 973-1011.
16. Burnstock G, Krugel U, Abbracchio MP, Illes P, (2011b). Purinergic signalling: from normal behaviour to pathological brain function. Prog Neurobiol 95: 229-274.
17. Charlton SJ, Vauquelin G, (2010). Elusive equilibrium: the challenge of interpreting receptor pharmacology using calcium assays. Br J Pharmacol 161: 1250-1265.
18. Chessell IP, Hatcher JP, Bountra C, Michel AD, Hughes JP, Green P, et al. (2005). Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain. Pain 114: 386-396.
19. Clark AK, Wodarski R, Guida F, Sasso O, Malcangio M, (2010). Cathepsin S release from primary cultured microglia is regulated by the P2X7 receptor. Glia 58: 1710-1726.
20. Coddou C, Yan Z, Obsil T, Huidobro-Toro JP, Stojilkovic SS, (2011). Activation and regulation of purinergic P2X receptor channels. Pharmacol Rev 63: 641-683.
21. Csolle C, Sperlagh B, (2010). Peripheral origin of IL-1beta production in the rodent hippocampus under in vivo systemic bacterial lipopolysaccharide (LPS) challenge and its regulation by P2X(7) receptors. J Neuroimmunol 219: 38-46.
22. Csolle C, Ando RD, Kittel A, Goloncser F, Baranyi M, Soproni K, et al. (2013). The absence of P2X7 receptors (P2rx7) on non-haematopoietic cells leads to selective alteration in mood-related behaviour with dysregulated gene expression and stress reactivity in mice. Int J Neuropsychopharmacol 16: 213-233.
23. Diaz-Hernandez JI, Gomez-Villafuertes R, Leon-Otegui M, Hontecillas-Prieto L, Del Puerto A, Trejo JL, et al. (2012). In vivo P2X7 inhibition reduces amyloid plaques in Alzheimer's disease through GSK3beta and secretases. Neurobiol Aging 33: 1816-1828.
24. Donnelly-Roberts DL, Namovic MT, Han P, Jarvis MF, (2009a). Mammalian P2X7 receptor pharmacology: comparison of recombinant mouse, rat and human P2X7 receptors. Br J Pharmacol 157: 1203-1214.
25. Donnelly-Roberts DL, Namovic MT, Surber B, Vaidyanathan SX, Perez-Medrano A, Wang Y, et al. (2009b). [(3)H]A-804598 ([(3)H]2-cyano-1-[(1S)-1-phenylethyl] -3-quinolin-5-ylguanidine) is a novel, potent, and selective antagonist radioligand for P2X7 receptors. Neuropharmacology 56: 223-229.
26. Duplantier AJ, Dombroski MA, Subramanyam C, Beaulieu AM, Chang SP, Gabel CA, et al. (2011). Optimization of the physicochemical and pharmacokinetic attributes in a 6-azauracil series of P2X7 receptor antagonists leading to the discovery of the clinical candidate CE-224,535. Bioorg Med Chem Lett 21: 3708-3711.
27. Engel T, Gomez-Villafuertes R, Tanaka K, Mesuret G, Sanz-Rodriguez A, Garcia-Huerta P, et al. (2012). Seizure suppression and neuroprotection by targeting the purinergic P2X7 receptor during status epilepticus in mice. FASEB J 26: 1616-1628.
28. Furber M, Alcaraz L, Bent JE, Beyerbach A, Bowers K, Braddock M, et al. (2007). Discovery of potent and selective adamantane-based small-molecule P2X(7) receptor antagonists/interleukin-1beta inhibitors. J Med Chem 50: 5882-5885.
29. Goshen I, Kreisel T, Ben-Menachem-Zidon O, Licht T, Weidenfeld J, Ben-Hur T, et al. (2008). Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression. Mol Psychiatry 13: 717-728.
30. Green EK, Grozeva D, Raybould R, Elvidge G, Macgregor S, Craig I, et al. (2009). P2RX7: a bipolar and unipolar disorder candidate susceptibility gene? Am J Med Genet B Neuropsychiatr Genet 150B: 1063-1069.
31. Grigoroiu-Serbanescu M, Herms S, Muhleisen TW, Georgi A, Diaconu CC, Strohmaier J, et al. (2009). Variation in P2RX7 candidate gene (rs2230912) is not associated with bipolar I disorder and unipolar major depression in four European samples. Am J Med Genet B Neuropsychiatr Genet 150B: 1017-1021.
32. Guile SD, Alcaraz L, Birkinshaw TN, Bowers KC, Ebden MR, Furber M, et al. (2009). Antagonists of the P2X(7) receptor. From lead identification to drug development. J Med Chem 52: 3123-3141.
33. Hattori M, Gouaux E, (2012). Molecular mechanism of ATP binding and ion channel activation in P2X receptors. Nature 485: 207-212.
34. Hejjas K, Szekely A, Domotor E, Halmai Z, Balogh G, Schilling B, et al. (2009). Association between depression and the Gln460Arg polymorphism of P2RX7 gene: a dimensional approach. Am J Med Genet B Neuropsychiatr Genet 150B: 295-299.
35. Iwata M, Li X, Ota KT, Banasr M, Sakaue F, Duman RS, (2012). Signaling pathways underlying the regulation of IL-1β in response to stress: targets for novel antidepressants. In: Society for Neuroscience Annual Meeting. New Orleans, LA.
36. Iwata M, Ota KT, Duman RS, (2013). The inflammasome: pathways linking psychological stress, depression, and systemic illnesses. Brain Behav Immun 31: 105-114.
37. Jones KA, Thomsen C, (2013). The role of the innate immune system in psychiatric disorders. Mol Cell Neurosci 53: 52-62.
38. Khairova RA, Machado-Vieira R, Du J, Manji HK, (2009). A potential role for pro-inflammatory cytokines in regulating synaptic plasticity in major depressive disorder. Int J Neuropsychopharmacol 12: 561-578.
39. Khakh BS, North RA, (2012). Neuromodulation by extracellular ATP and P2X receptors in the CNS. Neuron 76: 51-69.
40. Khansari PS, Sperlagh B, (2012). Inflammation in neurological and psychiatric diseases. Inflammopharmacology 20: 103-107.
41. Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG, (2010). Animal research: reporting in vivo experiments: the ARRIVE guidelines. Br J Pharmacol 160: 1577-1579.
42. Kim SH, Chung JM, (1992). An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 50: 355-363.
43. Koo JW, Duman RS, (2008). IL-1beta is an essential mediator of the antineurogenic and anhedonic effects of stress. Proc Natl Acad Sci U S A 105: 751-756.
44. Koo JW, Duman RS, (2009a). Evidence for IL-1 receptor blockade as a therapeutic strategy for the treatment of depression. Curr Opin Investig Drugs 10: 664-671.
45. Koo JW, Duman RS, (2009b). Interleukin-1 receptor null mutant mice show decreased anxiety-like behavior and enhanced fear memory. Neurosci Lett 456: 39-43.
46. Letavic MA, Lord B, Bischoff F, Hawryluk NA, Pieters S, Rech JC, et al. (2013). Synthesis and pharmacological characterization of two novel, brain penetrating P2X7 antagonists. ACS Med Chem Lett 4: 419-422.
47. Lucae S, Salyakina D, Barden N, Harvey M, Gagne B, Labbe M, et al. (2006). P2RX7, a gene coding for a purinergic ligand-gated ion channel, is associated with major depressive disorder. Hum Mol Genet 15: 2438-2445.
48. McGrath J, Drummond G, McLachlan E, Kilkenny C, Wainwright C, (2010). Guidelines for reporting experiments involving animals: the ARRIVE guidelines. Br J Pharmacol 160: 1573-1576.
49. McQuillin A, Bass NJ, Choudhury K, Puri V, Kosmin M, Lawrence J, et al. (2009). Case-control studies show that a non-conservative amino-acid change from a glutamine to arginine in the P2RX7 purinergic receptor protein is associated with both bipolar- and unipolar-affective disorders. Mol Psychiatry 14: 614-620.
50. Michel AD, Ng SW, Roman S, Clay WC, Dean DK, Walter DS, (2009). Mechanism of action of species-selective P2X(7) receptor antagonists. Br J Pharmacol 156: 1312-1325.
51. North RA, Jarvis MF, (2013). P2X receptors as drug targets. Mol Pharmacol 83: 759-769.
52. Rao JS, Harry GJ, Rapoport SI, Kim HW, (2010). Increased excitotoxicity and neuroinflammatory markers in postmortem frontal cortex from bipolar disorder patients. Mol Psychiatry 15: 384-392.
53. Sharp AJ, Polak PE, Simonini V, Lin SX, Richardson JC, Bongarzone ER, et al. (2008). P2x7 deficiency suppresses development of experimental autoimmune encephalomyelitis. J Neuroinflammation 5: 33.
54. Shiratori M, Tozaki-Saitoh H, Yoshitake M, Tsuda M, Inoue K, (2010). P2X7 receptor activation induces CXCL2 production in microglia through NFAT and PKC/MAPK pathways. J Neurochem 114: 810-819.
55. Soderlund J, Olsson SK, Samuelsson M, Walther-Jallow L, Johansson C, Erhardt S, et al. (2011). Elevation of cerebrospinal fluid interleukin-1ss in bipolar disorder. J Psychiatry Neurosci 36: 114-118.
56. Solle M, Labasi J, Perregaux DG, Stam E, Petrushova N, Koller BH, et al. (2001). Altered cytokine production in mice lacking P2X(7) receptors. J Biol Chem 276: 125-132.
57. Soronen P, Mantere O, Melartin T, Suominen K, Vuorilehto M, Rytsala H, et al. (2011). P2RX7 gene is associated consistently with mood disorders and predicts clinical outcome in three clinical cohorts. Am J Med Genet B Neuropsychiatr Genet 156B: 435-447.
58. Sperlagh B, Vizi ES, Wirkner K, Illes P, (2006). P2X7 receptors in the nervous system. Prog Neurobiol 78: 327-346.
59. Sperlagh B, Csolle C, Ando RD, Goloncser F, Kittel A, Baranyi M, (2012). The role of purinergic signaling in depressive disorders. Neuropsychopharmacol Hung 14: 231-238.
60. Stock TC, Bloom BJ, Wei N, Ishaq S, Park W, Wang X, et al. (2012). Efficacy and safety of CE-224,535, an antagonist of P2X7 receptor, in treatment of patients with rheumatoid arthritis inadequately controlled by methotrexate. J Rheumatol 39: 720-727.
61. Surprenant A, North RA, (2009). Signaling at purinergic P2X receptors. Annu Rev Physiol 71: 333-359.
62. Volonte C, Apolloni S, Skaper SD, Burnstock G, (2012). P2X7 receptors: channels, pores and more. CNS Neurol Disord Drug Targets 11: 705-721.
63. Young MT, Pelegrin P, Surprenant A, (2007). Amino acid residues in the P2X7 receptor that mediate differential sensitivity to ATP and BzATP. Mol Pharmacol 71: 92-100.