Generic placeholder image

Current Drug Targets

Author(s): Natiele C. da Silva Ferreira, Luiz A. Alves and Rômulo J. Soares-Bezerra*

DOI: 10.2174/1389450120666190213095923

DownloadDownload PDF Flyer Cite As
Potential Therapeutic Applications of P2 Receptor Antagonists: From Bench to Clinical Trials

Page: [919 - 937] Pages: 19

  • * (Excluding Mailing and Handling)

Abstract

Background: Extracellular purines and pyrimidines have important physiological functions in mammals. Purines and pyrimidines act on P1 and P2 purinergic receptors, which are widely expressed in the plasma membrane in various cell types. P2 receptors act as important therapeutic targets and are associated with several disorders, such as pain, neurodegeneration, cancer, inflammation, and thrombosis. However, the use of antagonists for P2 receptors in clinical therapy, with the exception of P2Y12, is a great challenge. Currently, many research groups and pharmaceutical companies are working on the development of specific antagonist molecules for each receptor subtype that could be used as new medicines to treat their respective disorders.

Objective: The present review compiles some interesting findings on the application of P2 receptor antagonists in different in vitro and in vivo experimental models as well as the progress of advanced clinical trials with these compounds.

Conclusion: Despite all of the exciting results obtained on the bench, few antagonists of P2 receptors advanced to the clinical trials, and once they reach this stage, the effectiveness of the therapy is not guaranteed, as in the example of P2X7 antagonists. Despite this, P2Y12 receptor antagonists have a history of success and have been used in therapy for at least two decades to prevent thrombosis in patients at risk for myocardial infarctions. This breakthrough is the motivation for scientists to develop new drugs with antagonistic activity for the other P2 receptors; thus, in a matter of years, we will have an evolution in the field of purinergic therapy.

Keywords: P2X receptors, P2Y receptors, antagonists, therapy, thrombosis, pain, inflammation, clinical trials.

Graphical Abstract

[1]
Ralevic V, Burnstock G. Receptors for purines and pyrimidines. Pharmacol Rev 1998; 50(3): 413-92.
[PMID: 9755289]
[2]
Fountain SJ. Primitive ATP-activated P2X receptors: discovery, function and pharmacology. Front Cell Neurosci 2013; 7: 247.
[http://dx.doi.org/10.3389/fncel.2013.00247] [PMID: 24367292]
[3]
Jacob F, Pérez Novo C, Bachert C, Van Crombruggen K. Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses. Purinergic Signal 2013; 9(3): 285-306.
[http://dx.doi.org/10.1007/s11302-013-9357-4] [PMID: 23404828]
[4]
Mutafova-Yambolieva VN, Durnin L. The purinergic neurotransmitter revisited: a single substance or multiple players? Pharmacol Ther 2014; 144(2): 162-91.
[http://dx.doi.org/10.1016/j.pharmthera.2014.05.012] [PMID: 24887688]
[5]
Hechler B, Gachet C. P2 receptors and platelet function. Purinergic Signal 2011; 7(3): 293-303.
[http://dx.doi.org/10.1007/s11302-011-9247-6] [PMID: 21792575]
[6]
Burnstock G. Purinergic receptors and pain. Curr Pharm Des 2009; 15(15): 1717-35.
[http://dx.doi.org/10.2174/138161209788186335] [PMID: 19442186]
[7]
Fredholm BB, Abbracchio MP, Burnstock G, et al. Nomenclature and classification of purinoceptors. Pharmacol Rev 1994; 46(2): 143-56.
[PMID: 7938164]
[8]
Thimm D, Knospe M, Abdelrahman A, et al. Characterization of new G protein-coupled adenine receptors in mouse and hamster. Purinergic Signal 2013; 9(3): 415-26.
[http://dx.doi.org/10.1007/s11302-013-9360-9] [PMID: 23608776]
[9]
Alves LA, de Melo Reis RA, de Souza CAM, et al. The P2X7 receptor: shifting from a low- to a high-conductance channel - an enigmatic phenomenon? Biochim Biophys Acta 2014; 1838(10): 2578-87.
[http://dx.doi.org/10.1016/j.bbamem.2014.05.015] [PMID: 24857862]
[10]
Chaumont S, Khakh BS. Patch-clamp coordinated spectroscopy shows P2X2 receptor permeability dynamics require cytosolic domain rearrangements but not Panx-1 channels. Proc Natl Acad Sci USA 2008; 105(33): 12063-8.
[http://dx.doi.org/10.1073/pnas.0803008105] [PMID: 18689682]
[11]
Bernier LP, Ase AR, Boué-Grabot E, Séguéla P. P2X4 receptor channels form large noncytolytic pores in resting and activated microglia. Glia 2012; 60(5): 728-37.
[http://dx.doi.org/10.1002/glia.22301] [PMID: 22318986]
[12]
Pelegrín P. Many ways to dilate the P2X7 receptor pore. Br J Pharmacol 2011; 163(5): 908-11.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01325.x] [PMID: 21410461]
[13]
Pelegrin P, Surprenant A. Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. EMBO J 2006; 25(21): 5071-82.
[http://dx.doi.org/10.1038/sj.emboj.7601378] [PMID: 17036048]
[14]
Faria RX, Defarias FP, Alves LA. Are second messengers crucial for opening the pore associated with P2X7 receptor? Am J Physiol Cell Physiol 2005; 288(2): C260-71.
[http://dx.doi.org/10.1152/ajpcell.00215.2004] [PMID: 15469955]
[15]
Jacobson KA, Boeynaems J-M. P2Y nucleotide receptors: promise of therapeutic applications. Drug Discov Today 2010; 15(13-14): 570-8.
[http://dx.doi.org/10.1016/j.drudis.2010.05.011] [PMID: 20594935]
[16]
von Kügelgen I. Pharmacological profiles of cloned mammalian P2Y-receptor subtypes. Pharmacol Ther 2006; 110(3): 415-32.
[http://dx.doi.org/10.1016/j.pharmthera.2005.08.014] [PMID: 16257449]
[17]
Coddou C, Yan Z, Obsil T, Huidobro-Toro JP, Stojilkovic SS. Activation and regulation of purinergic P2X receptor channels. Pharmacol Rev 2011; 63(3): 641-83.
[http://dx.doi.org/10.1124/pr.110.003129] [PMID: 21737531]
[18]
Wu JX, Xu MY, Miao XR, et al. Functional up-regulation of P2X3 receptors in dorsal root ganglion in a rat model of bone cancer pain. Eur J Pain 2012; 16(10): 1378-88.
[http://dx.doi.org/10.1002/j.1532-2149.2012.00149.x] [PMID: 22528605]
[19]
Burnstock G. Targeting the visceral purinergic system for pain control. Curr Opin Pharmacol 2012; 12(1): 80-6.
[http://dx.doi.org/ 10.1016/j.coph.2011.10.008] [PMID: 22036885]
[20]
Deiteren A, van der Linden L, de Wit A, et al. P2X3 receptors mediate visceral hypersensitivity during acute chemically-induced colitis and in the post-inflammatory phase via different mechanisms of sensitization. PLoS One 2015; 10(4): e0123810.
[http://dx.doi.org/10.1371/journal.pone.0123810] [PMID: 25885345]
[21]
Wang S, Zhu H-Y, Jin Y, et al. Adrenergic signaling mediates mechanical hyperalgesia through activation of P2X3 receptors in primary sensory neurons of rats with chronic pancreatitis. Am J Physiol Gastrointest Liver Physiol 2015; 308(8): G710-9.
[http://dx.doi.org/10.1152/ajpgi.00395.2014] [PMID: 25634810]
[22]
Zhang HP, Li CL, Lu P, et al. The function of P2X3 receptor and NK1 receptor antagonists on cyclophosphamide-induced cystitis in rats. World J Urol 2014; 32(1): 91-7.
[http://dx.doi.org/ 10.1007/s00345-013-1098-z] [PMID: 23666265]
[23]
Ito K, Iwami A, Katsura H, Ikeda M. Therapeutic effects of the putative P2X3/P2X2/3 antagonist A-317491 on cyclophosphamide-induced cystitis in rats. Naunyn Schmiedebergs Arch Pharmacol 2008; 377(4-6): 483-90.
[http://dx.doi.org/10.1007/s00210-007-0197-z] [PMID: 17917716]
[24]
Tsuda M, Shigemoto-Mogami Y, Koizumi S, et al. P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature 2003; 424(6950): 778-83.
[http://dx.doi.org/10.1038/nature01786] [PMID: 12917686]
[25]
Masuda T, Iwamoto S, Yoshinaga R, et al. Transcription factor IRF5 drives P2X4R+-reactive microglia gating neuropathic pain. Nat Commun 2014; 5: 3771.
[http://dx.doi.org/10.1038/ncomms4771] [PMID: 24818655]
[26]
Tsuda M, Tozaki-Saitoh H, Masuda T, et al. Lyn tyrosine kinase is required for P2X(4) receptor upregulation and neuropathic pain after peripheral nerve injury. Glia 2008; 56(1): 50-8.
[http://dx.doi.org/10.1002/glia.20591] [PMID: 17918263]
[27]
Tsuda M, Kuboyama K, Inoue T, Nagata K, Tozaki-Saitoh H, Inoue K. Behavioral phenotypes of mice lacking purinergic P2X4 receptors in acute and chronic pain assays. Mol Pain 2009; 5: 28.
[http://dx.doi.org/10.1186/1744-8069-5-28] [PMID: 19515262]
[28]
Teixeira JM, de Oliveira-Fusaro MCG, Parada CA, Tambeli CH. Peripheral P2X7 receptor-induced mechanical hyperalgesia is mediated by bradykinin. Neuroscience 2014; 277: 163-73.
[http://dx.doi.org/10.1016/j.neuroscience.2014.06.057] [PMID: 24997266]
[29]
Ochi-ishi R, Nagata K, Inoue T, Tozaki-Saitoh H, Tsuda M, Inoue K. Involvement of the chemokine CCL3 and the purinoceptor P2X7 in the spinal cord in paclitaxel-induced mechanical allodynia. Mol Pain 2014; 10(1): 53.
[PMID: 25127716]
[30]
Ying YL, Wei XH, Xu XB, et al. Over-expression of P2X7 receptors in spinal glial cells contributes to the development of chronic postsurgical pain induced by skin/muscle incision and retraction (SMIR) in rats. Exp Neurol 2014; 261: 836-43.
[http://dx.doi.org/10.1016/j.expneurol.2014.09.007] [PMID: 25242211]
[31]
Broom DC, Matson DJ, Bradshaw E, et al. Characterization of N-(adamantan-1-ylmethyl)-5-[(3R-amino-pyrrolidin-1-yl)methyl]-2-chloro-benzamide, a P2X7 antagonist in animal models of pain and inflammation. J Pharmacol Exp Ther 2008; 327(3): 620-33.
[http://dx.doi.org/10.1124/jpet.108.141853] [PMID: 18772321]
[32]
Honore P, Donnelly-Roberts D, Namovic MT, et al. A-740003 [N-(1-[(cyanoimino)(5-quinolinylamino) methyl]amino-2,2-dimethylpropyl)-2-(3,4-dimethoxyphenyl)acetamide], a novel and selective P2X7 receptor antagonist, dose-dependently reduces neuropathic pain in the rat. J Pharmacol Exp Ther 2006; 319(3): 1376-85.
[http://dx.doi.org/10.1124/jpet.106.111559] [PMID: 16982702]
[33]
Munoz FM, Gao R, Tian Y, Henstenburg BA, Barrett JE, Hu H. Neuronal P2X7 receptor-induced reactive oxygen species production contributes to nociceptive behavior in mice. Sci Rep 2017; 7(1): 3539.
[http://dx.doi.org/10.1038/s41598-017-03813-7] [PMID: 28615626]
[34]
Chen J, Wang L, Zhang Y, Yang J. P2Y1 purinoceptor inhibition reduces extracellular signal-regulated protein kinase 1/2 phosphorylation in spinal cord and dorsal root ganglia: implications for cancer-induced bone pain. Acta Biochim Biophys Sin (Shanghai) 2012; 44(4): 367-72.
[http://dx.doi.org/10.1093/abbs/gms007] [PMID: 22349022]
[35]
Kwon S-G, Roh D-H, Yoon S-Y, et al. Acid evoked thermal hyperalgesia involves peripheral P2Y1 receptor mediated TRPV1 phosphorylation in a rodent model of thrombus induced ischemic pain. Mol Pain 2014; 10(1): 2.
[http://dx.doi.org/10.1186/1744-8069-10-2] [PMID: 24401144]
[36]
Li N, Lu ZY, Yu LH, Burnstock G, Deng XM, Ma B. Inhibition of G protein-coupled P2Y2 receptor induced analgesia in a rat model of trigeminal neuropathic pain. Mol Pain 2014; 10(1): 21.
[http://dx.doi.org/10.1186/1744-8069-10-21] [PMID: 24642246]
[37]
Magni G, Merli D, Verderio C, Abbracchio MP, Ceruti S. P2Y2 receptor antagonists as anti-allodynic agents in acute and sub-chronic trigeminal sensitization: role of satellite glial cells. Glia 2015; 63(7): 1256-69.
[http://dx.doi.org/10.1002/glia.22819] [PMID: 25779655]
[38]
Barragán-Iglesias P, Pineda-Farias JB, Cervantes-Durán C, et al. Role of spinal P2Y6 and P2Y11 receptors in neuropathic pain in rats: possible involvement of glial cells. Mol Pain 2014; 10: 29.
[http://dx.doi.org/10.1186/1744-8069-10-29] [PMID: 24886406]
[39]
Kobayashi K, Yamanaka H, Yanamoto F, Okubo M, Noguchi K. Multiple P2Y subtypes in spinal microglia are involved in neuropathic pain after peripheral nerve injury. Glia 2012; 60(10): 1529-39.
[http://dx.doi.org/10.1002/glia.22373] [PMID: 22736439]
[40]
Barragán-Iglesias P, Mendoza-Garcés L, Pineda-Farias JB, et al. Participation of peripheral P2Y1, P2Y6 and P2Y11 receptors in formalin-induced inflammatory pain in rats. Pharmacol Biochem Behav 2015; 128: 23-32.
[http://dx.doi.org/10.1016/j.pbb. 2014.11.001] [PMID: 25449358]
[41]
Huang D, Yang J, Liu X, et al. P2Y6 receptor activation is involved in the development of neuropathic pain induced by chronic constriction injury of the sciatic nerve in rats. J Clin Neurosci 2018; 56: 156-62.
[http://dx.doi.org/10.1016/j.jocn.2018.07.013] [PMID: 30045810]
[42]
Horváth G, Gölöncsér F, Csölle C, et al. Central P2Y12 receptor blockade alleviates inflammatory and neuropathic pain and cytokine production in rodents. Neurobiol Dis 2014; 70: 162-78.
[http://dx.doi.org/10.1016/j.nbd.2014.06.011] [PMID: 24971933]
[43]
Jia T, Rao J, Zou L, et al. Nanoparticle-encapsulated curcumin inhibits diabetic neuropathic pain involving the P2Y12 receptor in the dorsal root ganglia. Front Neurosci 2018; 11: 755.
[http://dx.doi.org/10.3389/fnins.2017.00755] [PMID: 29422835]
[44]
Jacobson KA, Costanzi S, Joshi BV, Besada P, Shin DH, Ko H, et al. Agonists and antagonists for P2 receptors. Novartis Found Symp 2006. 276: 58-68-72, 107-12, 275-81.
[http://dx.doi.org/10.1002/9780470032244.ch6]
[45]
Chauhan PS, Singh DK, Dash D, Singh R. Intranasal curcumin regulates chronic asthma in mice by modulating NF-ĸB activation and MAPK signaling. Phytomedicine 2018; 51: 29-38.
[http://dx.doi.org/10.1016/j.phymed.2018.06.022] [PMID: 30466625]
[46]
Mesuret G, Engel T, Hessel EV, et al. P2X7 receptor inhibition interrupts the progression of seizures in immature rats and reduces hippocampal damage. CNS Neurosci Ther 2014; 20(6): 556-64.
[http://dx.doi.org/10.1111/cns.12272] [PMID: 24750893]
[47]
Jimenez-Pacheco A, Diaz-Hernandez M, Arribas-Blázquez M, et al. Transient P2X7 receptor antagonism produces lasting reductions in spontaneous seizures and gliosis in experimental temporal lobe epilepsy. J Neurosci 2016; 36(22): 5920-32.
[http://dx.doi.org/ 10.1523/JNEUROSCI.4009-15.2016] [PMID: 27251615]
[48]
Huang C, Chi XS, Li R, et al. Inhibition of P2X7 receptor ameliorates nuclear factor-kappa B mediated neuroinflammation induced by status epilepticus in rat hippocampus. J Mol Neurosci 2017; 63(2): 173-84.
[http://dx.doi.org/10.1007/s12031-017-0968-z] [PMID: 28856625]
[49]
Gandelman M, Levy M, Cassina P, Barbeito L, Beckman JS. P2X7 receptor-induced death of motor neurons by a peroxynitrite/FAS-dependent pathway. J Neurochem 2013; 126(3): 382-8.
[http://dx.doi.org/10.1111/jnc.12286] [PMID: 23646980]
[50]
Apolloni S, Amadio S, Parisi C, et al. Spinal cord pathology is ameliorated by P2X7 antagonism in a SOD1-mutant mouse model of amyotrophic lateral sclerosis. Dis Model Mech 2014; 7(9): 1101-9.
[http://dx.doi.org/10.1242/dmm.017038] [PMID: 25038061]
[51]
Gandelman M, Peluffo H, Beckman JS, Cassina P, Barbeito L. Extracellular ATP and the P2X7 receptor in astrocyte-mediated motor neuron death: implications for amyotrophic lateral sclerosis. J Neuroinflammation 2010; 7: 33.
[http://dx.doi.org/10.1186/1742-2094-7-33] [PMID: 20534165]
[52]
Tsimis ME, Lei J, Rosenzweig JM, et al. P2X7 receptor blockade prevents preterm birth and perinatal brain injury in a mouse model of intrauterine inflammation. Biol Reprod 2017; 97(2): 230-9.
[http://dx.doi.org/10.1093/biolre/iox081] [PMID: 29044426]
[53]
Carmo MRS, Menezes APF, Nunes ACL, et al. The P2X7 receptor antagonist Brilliant Blue G attenuates contralateral rotations in a rat model of Parkinsonism through a combined control of synaptotoxicity, neurotoxicity and gliosis. Neuropharmacology 2014; 81: 142-52.
[http://dx.doi.org/10.1016/j.neuropharm.2014.01.045] [PMID: 24508709]
[54]
Ni J, Wang P, Zhang J, Chen W, Gu L. Silencing of the P2X(7) receptor enhances amyloid-β phagocytosis by microglia. Biochem Biophys Res Commun 2013; 434(2): 363-9.
[http://dx.doi.org/ 10.1016/j.bbrc.2013.03.079] [PMID: 23562658]
[55]
Delarasse C, Auger R, Gonnord P, Fontaine B, Kanellopoulos JM. The purinergic receptor P2X7 triggers α-secretase-dependent processing of the amyloid precursor protein. J Biol Chem 2011; 286(4): 2596-606.
[http://dx.doi.org/10.1074/jbc.M110.200618] [PMID: 21081501]
[56]
Lee HG, Won SM, Gwag BJ, Lee YB. Microglial P2X7 receptor expression is accompanied by neuronal damage in the cerebral cortex of the APPswe/PS1dE9 mouse model of Alzheimer’s disease. Exp Mol Med 2011; 43(1): 7-14.
[http://dx.doi.org/ 10.3858/emm.2011.43.1.001] [PMID: 21088470]
[57]
León-Otegui M, Gómez-Villafuertes R, Díaz-Hernández JI, Díaz-Hernández M, Miras-Portugal MT, Gualix J. Opposite effects of P2X7 and P2Y2 nucleotide receptors on α-secretase-dependent APP processing in Neuro-2a cells. FEBS Lett 2011; 585(14): 2255-62.
[http://dx.doi.org/10.1016/j.febslet.2011.05.048] [PMID: 21651910]
[58]
Diaz-Hernandez JI, Gomez-Villafuertes R, León-Otegui M, et al. In vivo P2X7 inhibition reduces amyloid plaques in Alzheimer’s disease through GSK3β and secretases. Neurobiol Aging 2012; 33(8): 1816-28.
[http://dx.doi.org/10.1016/j.neurobiolaging.2011. 09.040] [PMID: 22048123]
[59]
Sanz JM, Chiozzi P, Ferrari D, et al. Activation of microglia by amyloid beta requires P2X7 receptor expression. J Immunol 2009; 182(7): 4378-85.
[http://dx.doi.org/10.4049/jimmunol.0803612] [PMID: 19299738]
[60]
Chen X, Hu J, Jiang L, et al. Brilliant Blue G improves cognition in an animal model of Alzheimer’s disease and inhibits amyloid-β-induced loss of filopodia and dendrite spines in hippocampal neurons. Neuroscience 2014; 279: 94-101.
[http://dx.doi.org/10.1016/j.neuroscience.2014.08.036] [PMID: 25193238]
[61]
Delekate A, Füchtemeier M, Schumacher T, Ulbrich C, Foddis M, Petzold GC. Metabotropic P2Y1 receptor signalling mediates astrocytic hyperactivity in vivo in an Alzheimer’s disease mouse model. Nat Commun 2014; 5: 5422.
[http://dx.doi.org/ 10.1038/ncomms6422] [PMID: 25406732]
[62]
North RA, Jarvis MF. P2X receptors as drug targets. Mol Pharmacol 2013; 83(4): 759-69.
[http://dx.doi.org/10.1124/mol. 112.083758] [PMID: 23253448]
[63]
Beigi RD, Kertesy SB, Aquilina G, Dubyak GR. Oxidized ATP (oATP) attenuates proinflammatory signaling via P2 receptor-independent mechanisms. Br J Pharmacol 2003; 140(3): 507-19.
[http://dx.doi.org/10.1038/sj.bjp.0705470] [PMID: 14522842]
[64]
Pellegatti P, Raffaghello L, Bianchi G, Piccardi F, Pistoia V, Di Virgilio F. Increased level of extracellular ATP at tumor sites: in vivo imaging with plasma membrane luciferase. PLoS One 2008; 3(7): e2599.
[http://dx.doi.org/10.1371/journal.pone.0002599] [PMID: 18612415]
[65]
Ryu JK, Jantaratnotai N, Serrano-Perez MC, McGeer PL, McLarnon JG. Block of purinergic P2X7R inhibits tumor growth in a C6 glioma brain tumor animal model. J Neuropathol Exp Neurol 2011; 70(1): 13-22.
[http://dx.doi.org/10.1097/NEN.0b013e 318201d4d4] [PMID: 21157381]
[66]
Qiu Y, Li WH, Zhang HQ, Liu Y, Tian XX, Fang WG. P2X7 mediates ATP-driven invasiveness in prostate cancer cells. PLoS One 2014; 9(12): e114371.
[http://dx.doi.org/10.1371/journal.pone. 0114371] [PMID: 25486274]
[67]
Giannuzzo A, Pedersen SF, Novak I. The P2X7 receptor regulates cell survival, migration and invasion of pancreatic ductal adenocarcinoma cells. Mol Cancer 2015; 14(1): 203.
[http://dx.doi.org/ 10.1186/s12943-015-0472-4] [PMID: 26607222]
[68]
Takai E, Tsukimoto M, Harada H, Kojima S. Autocrine signaling via release of ATP and activation of P2X7 receptor influences motile activity of human lung cancer cells. Purinergic Signal 2014; 10(3): 487-97.
[http://dx.doi.org/10.1007/s11302-014-9411-x] [PMID: 24627191]
[69]
Xia J, Yu X, Tang L, Li G, He T. P2X7 receptor stimulates breast cancer cell invasion and migration via the AKT pathway. Oncol Rep 2015; 34(1): 103-10.
[http://dx.doi.org/10.3892/or.2015.3979] [PMID: 25976617]
[70]
Hattori F, Ohshima Y, Seki S, et al. Feasibility study of B16 melanoma therapy using oxidized ATP to target purinergic receptor P2X7. Eur J Pharmacol 2012; 695(1-3): 20-6.
[http://dx.doi.org/ 10.1016/j.ejphar.2012.09.001] [PMID: 22981895]
[71]
Amoroso F, Salaro E, Falzoni S, et al. P2X7 targeting inhibits growth of human mesothelioma. Oncotarget 2016; 7(31): 49664-76.
[http://dx.doi.org/10.18632/oncotarget.10430] [PMID: 27391069]
[72]
Zhou JZ, Riquelme MA, Gao X, Ellies LG, Sun LZ, Jiang JX. Differential impact of adenosine nucleotides released by osteocytes on breast cancer growth and bone metastasis. Oncogene 2015; 34(14): 1831-42.
[http://dx.doi.org/10.1038/onc.2014.113] [PMID: 24837364]
[73]
Fang J, Chen X, Zhang L, et al. P2X7R suppression promotes glioma growth through epidermal growth factor receptor signal pathway. Int J Biochem Cell Biol 2013; 45(6): 1109-20.
[http://dx.doi.org/10.1016/j.biocel.2013.03.005] [PMID: 23523696]
[74]
Xie R, Xu J, Wen G, et al. The P2Y2 nucleotide receptor mediates the proliferation and migration of human hepatocellular carcinoma cells induced by ATP. J Biol Chem 2014; 289(27): 19137-49.
[http://dx.doi.org/10.1074/jbc.M113.540047] [PMID: 24847054]
[75]
Jin H, Eun SY, Lee JSJH, et al. P2Y2 receptor activation by nucleotides released from highly metastatic breast cancer cells increases tumor growth and invasion via crosstalk with endothelial cells. Breast Cancer Res 2014; 16(5): R77.
[http://dx.doi.org/ 10.1186/bcr3694] [PMID: 25156554]
[76]
Li W-H, Qiu Y, Zhang H-Q, et al. P2Y2 receptor promotes cell invasion and metastasis in prostate cancer cells. Br J Cancer 2013; 109(6): 1666-75.
[http://dx.doi.org/10.1038/bjc.2013.484] [PMID: 23969730]
[77]
Chadet S, Jelassi B, Wannous R, et al. The activation of P2Y2 receptors increases MCF-7 breast cancer cells migration through the MEK-ERK1/2 signalling pathway. Carcinogenesis 2014; 35(6): 1238-47.
[http://dx.doi.org/10.1093/carcin/bgt493] [PMID: 24390819]
[78]
Choi JH, Ji YG, Lee DH. Uridine triphosphate increases proliferation of human cancerous pancreatic duct epithelial cells by activating P2Y2 receptor. Pancreas 2013; 42(4): 680-6.
[http://dx.doi.org/10.1097/MPA.0b013e318271bb4b] [PMID: 23462325]
[79]
Placet M, Arguin G, Molle CM, et al. The G protein-coupled P2Y6 receptor promotes colorectal cancer tumorigenesis by inhibiting apoptosis. Biochim Biophys Acta Mol Basis Dis 2018; 1864(5 Pt A): 1539-51.
[http://dx.doi.org/10.1016/j.bbadis.2018.02.008] [PMID: 29454075]
[80]
Khalid M, Brisson L, Tariq M, et al. Carcinoma-specific expression of P2Y11 receptor and its contribution in ATP-induced purinergic signalling and cell migration in human hepatocellular carcinoma cells. Oncotarget 2017; 8(23): 37278-90.
[http://dx.doi.org/10.18632/oncotarget.16191] [PMID: 28418839]
[81]
Cho MS, Noh K, Haemmerle M, et al. Role of ADP receptors on platelets in the growth of ovarian cancer. Blood 2017; 130(10): 1235-42.
[http://dx.doi.org/10.1182/blood-2017-02-769893] [PMID: 28679740]
[82]
Gebremeskel S, LeVatte T, Liwski RS, Johnston B, Bezuhly M. The reversible P2Y12 inhibitor ticagrelor inhibits metastasis and improves survival in mouse models of cancer. Int J Cancer 2015; 136(1): 234-40.
[http://dx.doi.org/10.1002/ijc.28947] [PMID: 24798403]
[83]
Sarangi S, Pandey A, Papa A-L, et al. P2Y12 receptor inhibition augments cytotoxic effects of cisplatin in breast cancer. Med Oncol 2013; 30(2): 567.
[http://dx.doi.org/10.1007/s12032-013-0567-y] [PMID: 23568163]
[84]
Li F, Guo N, Ma Y, Ning B, Wang Y, Kou L. Inhibition of P2X4 suppresses joint inflammation and damage in collagen-induced arthritis. Inflammation 2014; 37(1): 146-53.
[http://dx.doi.org/ 10.1007/s10753-013-9723-y] [PMID: 24062058]
[85]
Li F, Wang L, Li J-W, et al. Hypoxia induced amoeboid microglial cell activation in postnatal rat brain is mediated by ATP receptor P2X4. BMC Neurosci 2011; 12(1): 111.
[http://dx.doi.org/ 10.1186/1471-2202-12-111] [PMID: 22053919]
[86]
Vázquez-Villoldo N, Domercq M, Martín A, Llop J, Gómez-Vallejo V, Matute C. P2X4 receptors control the fate and survival of activated microglia. Glia 2014; 62(2): 171-84.
[http://dx.doi.org/ 10.1002/glia.22596] [PMID: 24254916]
[87]
Ulmann L, Hirbec H, Rassendren F. P2X4 receptors mediate PGE2 release by tissue-resident macrophages and initiate inflammatory pain. EMBO J 2010; 29(14): 2290-300.
[http://dx.doi.org/ 10.1038/emboj.2010.126] [PMID: 20562826]
[88]
Zech A, Wiesler B, Ayata CK, et al. P2rx4 deficiency in mice alleviates allergen-induced airway inflammation. Oncotarget 2016; 7(49): 80288-97.
[http://dx.doi.org/10.18632/oncotarget.13375] [PMID: 27863396]
[89]
Wright A, Mahaut-Smith M, Symon F, et al. Impaired P2X1 receptor-mediated adhesion in eosinophils from asthmatic patients. J Immunol 2016; 196(12): 4877-84.
[http://dx.doi.org/10.4049/jimmunol.1501585] [PMID: 27183585]
[90]
Alberto AVP, Faria RX, de Menezes JRL, et al. Role of P2 receptors as modulators of rat eosinophil recruitment in allergic inflammation. PLoS One 2016; 11(1): e0145392.
[http://dx.doi.org/ 10.1371/journal.pone.0145392] [PMID: 26784445]
[91]
Zhao J, Wang H, Dai C, et al. P2X7 blockade attenuates murine lupus nephritis by inhibiting activation of the NLRP3/ASC/caspase 1 pathway. Arthritis Rheum 2013; 65(12): 3176-85.
[http://dx.doi.org/10.1002/art.38174] [PMID: 24022661]
[92]
Zhang Y, Yuan F, Cao X, et al. P2X7 receptor blockade protects against cisplatin-induced nephrotoxicity in mice by decreasing the activities of inflammasome components, oxidative stress and caspase-3. Toxicol Appl Pharmacol 2014; 281(1): 1-10.
[http://dx.doi.org/10.1016/j.taap.2014.09.016] [PMID: 25308879]
[93]
Monção-Ribeiro LC, Faffe DS, Santana PT, et al. P2X7 receptor modulates inflammatory and functional pulmonary changes induced by silica. PLoS One 2014; 9(10): e110185.
[http://dx.doi.org/10.1371/journal.pone.0110185] [PMID: 25310682]
[94]
Lucattelli M, Cicko S, Müller T, et al. P2X7 receptor signaling in the pathogenesis of smoke-induced lung inflammation and emphysema. Am J Respir Cell Mol Biol 2011; 44(3): 423-9.
[http://dx.doi.org/10.1165/rcmb.2010-0038OC] [PMID: 20508069]
[95]
Riteau N, Gasse P, Fauconnier L, et al. Extracellular ATP is a danger signal activating P2X7 receptor in lung inflammation and fibrosis. Am J Respir Crit Care Med 2010; 182(6): 774-83.
[http://dx.doi.org/10.1164/rccm.201003-0359OC] [PMID: 20522787]
[96]
Wan P, Liu X, Xiong Y, et al. Extracellular ATP mediates inflammatory responses in colitis via P2 × 7 receptor signaling. Sci Rep 2016; 6: 19108.
[http://dx.doi.org/10.1038/srep19108] [PMID: 26739809]
[97]
Marques CC, Castelo-Branco MT, Pacheco RG, et al. Prophylactic systemic P2X7 receptor blockade prevents experimental colitis. Biochim Biophys Acta 2014; 1842(1): 65-78.
[http://dx.doi.org/10.1016/j.bbadis.2013.10.012] [PMID: 24184714]
[98]
da Silva GL, Sperotto NDM, Borges TJ, et al. P2X7 receptor is required for neutrophil accumulation in a mouse model of irritant contact dermatitis. Exp Dermatol 2013; 22(3): 184-8.
[http://dx.doi.org/10.1111/exd.12094] [PMID: 23489421]
[99]
Huang C, Yu W, Cui H, et al. P2X7 blockade attenuates mouse liver fibrosis. Mol Med Rep 2014; 9(1): 57-62.
[http://dx.doi.org/10.3892/mmr.2013.1807] [PMID: 24247209]
[100]
McInnes IB, Cruwys S, Bowers K, Braddock M. Targeting the P2X7 receptor in rheumatoid arthritis: biological rationale for P2X7 antagonism. Clin Exp Rheumatol 2014; 32(6): 878-82.
[PMID: 25288220]
[101]
Teixeira JM, Dias EV, Parada CA, Tambeli CH. Intra-articular blockade of P2X7 receptor reduces the articular hyperalgesia and inflammation in the knee joint synovitis especially in female rats. J Pain 2017; 18(2): 132-43.
[http://dx.doi.org/10.1016/j.jpain.2016. 10.008] [PMID: 27818192]
[102]
Bhattacharya A, Wang Q, Ao H, et al. Pharmacological characterization of a novel centrally permeable P2X7 receptor antagonist: JNJ-47965567. Br J Pharmacol 2013; 170(3): 624-40.
[http://dx.doi.org/10.1111/bph.12314] [PMID: 23889535]
[103]
Danquah W, Meyer-Schwesinger C, Rissiek B, et al. Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation. Sci Transl Med 2016; 8(366): 366ra162.
[http://dx.doi.org/10.1126/scitranslmed.aaf8463] [PMID: 27881823]
[104]
Amison RT, Momi S, Morris A, et al. RhoA signaling through platelet P2Y1 receptor controls leukocyte recruitment in allergic mice. J Allergy Clin Immunol 2015; 135(2): 528-38.
[http://dx.doi.org/10.1016/j.jaci.2014.09.032] [PMID: 25445826]
[105]
Amison RT, Arnold S, O’Shaughnessy BG, et al. Lipopolysaccharide (LPS) induced pulmonary neutrophil recruitment and platelet activation is mediated via the P2Y1 and P2Y14 receptors in mice. Pulm Pharmacol Ther 2017; 45: 62-8.
[http://dx.doi.org/ 10.1016/j.pupt.2017.05.005] [PMID: 28487256]
[106]
Degagné E, Grbic DM, Dupuis A-A, et al. P2Y2 receptor transcription is increased by NF-kappa B and stimulates cyclooxygenase-2 expression and PGE2 released by intestinal epithelial cells. J Immunol 2009; 183(7): 4521-9.
[http://dx.doi.org/10.4049/jimmunol.0803977] [PMID: 19734210]
[107]
Zhang Y, Kohan DE, Nelson RD, Carlson NG, Kishore BK. Potential involvement of P2Y2 receptor in diuresis of postobstructive uropathy in rats. Am J Physiol Renal Physiol 2010; 298(3): F634-42.
[http://dx.doi.org/10.1152/ajprenal.00382.2009] [PMID: 20007349]
[108]
Vanderstocken G, Bondue B, Horckmans M, et al. P2Y2 receptor regulates VCAM-1 membrane and soluble forms and eosinophil accumulation during lung inflammation. J Immunol 2010; 185(6): 3702-7.
[http://dx.doi.org/10.4049/jimmunol.0903908] [PMID: 20720203]
[109]
Ayata CK, Ganal SC, Hockenjos B, et al. Purinergic P2Y2 receptors promote neutrophil infiltration and hepatocyte death in mice with acute liver injury. Gastroenterology 2012; 143(6): 1620-1629.e4.
[http://dx.doi.org/10.1053/j.gastro.2012.08.049] [PMID: 22974709]
[110]
Inoue Y, Chen Y, Hirsh MI, Yip L, Junger WG. A3 and P2Y2 receptors control the recruitment of neutrophils to the lungs in a mouse model of sepsis. Shock 2008; 30(2): 173-7.
[PMID: 18091570]
[111]
Eun SY, Park SW, Lee JH, Chang KC, Kim HJ. P2Y(2)R activation by nucleotides released from oxLDL-treated endothelial cells (ECs) mediates the interaction between ECs and immune cells through RAGE expression and reactive oxygen species production. Free Radic Biol Med 2014; 69: 157-66.
[http://dx.doi.org/10.1016/j.freeradbiomed.2014.01.022] [PMID: 24486339]
[112]
Eun SY, Seo J, Park SW, Lee JH, Chang KC, Kim HJ. LPS potentiates nucleotide-induced inflammatory gene expression in macrophages via the upregulation of P2Y2 receptor. Int Immunopharmacol 2014; 18(2): 270-6.
[http://dx.doi.org/10.1016/j.intimp.2013. 11.026] [PMID: 24316256]
[113]
Paniagua-Herranz L, Gil-Redondo JC, Queipo MJ, et al. Prostaglandin E2 impairs P2Y2/P2Y4 receptor signaling in cerebellar astrocytes via EP3 receptors. Front Pharmacol 2017; 8: 937.
[http://dx.doi.org/10.3389/fphar.2017.00937] [PMID: 29311938]
[114]
Grbic DM, Degagné É, Larrivée J-F, et al. P2Y6 receptor contributes to neutrophil recruitment to inflamed intestinal mucosa by increasing CXC chemokine ligand 8 expression in an AP-1-dependent manner in epithelial cells. Inflamm Bowel Dis 2012; 18(8): 1456-69.
[http://dx.doi.org/10.1002/ibd.21931] [PMID: 22095787]
[115]
Hao Y, Liang JF, Chow AW, Cheung WT, Ko WH. P2Y6 receptor-mediated proinflammatory signaling in human bronchial epithelia. PLoS One 2014; 9(9): e106235.
[http://dx.doi.org/10.1371/journal.pone.0106235] [PMID: 25243587]
[116]
Vieira RP, Müller T, Grimm M, et al. Purinergic receptor type 6 contributes to airway inflammation and remodeling in experimental allergic airway inflammation. Am J Respir Crit Care Med 2011; 184(2): 215-23.
[http://dx.doi.org/10.1164/rccm.201011-1762OC] [PMID: 21512170]
[117]
Uratsuji H, Tada Y, Kawashima T, et al. P2Y6 receptor signaling pathway mediates inflammatory responses induced by monosodium urate crystals. J Immunol 2012; 188(1): 436-44.
[http://dx.doi.org/ 10.4049/jimmunol.1003746] [PMID: 22102722]
[118]
Sil P, Hayes CP, Reaves BJ, et al. P2Y6 receptor antagonist MRS2578 inhibits neutrophil activation and aggregated neutrophil extracellular trap formation induced by gout-associated monosodium urate crystals. J Immunol 2017; 198(1): 428-42.
[http://dx.doi.org/10.4049/jimmunol.1600766] [PMID: 27903742]
[119]
Garcia RA, Yan M, Search D, et al. P2Y6 receptor potentiates pro-inflammatory responses in macrophages and exhibits differential roles in atherosclerotic lesion development. PLoS One 2014; 9(10): e111385.
[http://dx.doi.org/10.1371/journal.pone.0111385] [PMID: 25360548]
[120]
Liverani E, Rico MC, Tsygankov AY, Kilpatrick LE, Kunapuli SP. P2Y12 receptor modulates sepsis-induced inflammation. Arterioscler Thromb Vasc Biol 2016; 36(5): 961-71.
[http://dx.doi.org/ 10.1161/ATVBAHA.116.307401] [PMID: 27055904]
[121]
Satonaka H, Nagata D, Takahashi M, et al. Involvement of P2Y12 receptor in vascular smooth muscle inflammatory changes via MCP-1 upregulation and monocyte adhesion. Am J Physiol Heart Circ Physiol 2015; 308(8): H853-61.
[http://dx.doi.org/10.1152/ajpheart.00862.2013] [PMID: 25681429]
[122]
Ishimaru M, Yusuke N, Tsukimoto M, et al. Purinergic signaling via P2Y receptors up-mediates IL-6 production by liver macrophages/Kupffer cells. J Toxicol Sci 2014; 39(3): 413-23.
[http://dx.doi.org/10.2131/jts.39.413] [PMID: 24849676]
[123]
Barrett MO, Sesma JI, Ball CB, et al. A selective high-affinity antagonist of the P2Y14 receptor inhibits UDP-glucose-stimulated chemotaxis of human neutrophils. Mol Pharmacol 2013; 84(1): 41-9.
[http://dx.doi.org/10.1124/mol.113.085654] [PMID: 23592514]
[124]
Azroyan A, Cortez-Retamozo V, Bouley R, et al. Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor. PLoS One 2015; 10(3): e0121419.
[http://dx.doi.org/10.1371/journal.pone.0121419] [PMID: 25799465]
[125]
Hechler B, Lenain N, Marchese P, et al. A role of the fast ATP-gated P2X1 cation channel in thrombosis of small arteries in vivo. J Exp Med 2003; 198(4): 661-7.
[http://dx.doi.org/10.1084/jem.20030144] [PMID: 12913094]
[126]
Labarthe B, Babin J, Bryckaert M, Théroux P, Bonnefoy A. Effects of P2Y(1) receptor antagonism on the reactivity of platelets from patients with stable coronary artery disease using aspirin and clopidogrel. Br J Pharmacol 2012; 166(1): 221-31.
[http://dx.doi.org/ 10.1111/j.1476-5381.2011.01683.x] [PMID: 21950486]
[127]
Lenain N, Freund M, Léon C, Cazenave J-P, Gachet C. Inhibition of localized thrombosis in P2Y1-deficient mice and rodents treated with MRS2179, a P2Y1 receptor antagonist. J Thromb Haemost 2003; 1(6): 1144-9.
[http://dx.doi.org/10.1046/j.1538-7836.2003. 00144.x] [PMID: 12871312]
[128]
Léon C, Freund M, Ravanat C, Baurand A, Cazenave JP, Gachet C. Key role of the P2Y(1) receptor in tissue factor-induced thrombin-dependent acute thromboembolism: studies in P2Y(1)-knockout mice and mice treated with a P2Y(1) antagonist. Circulation 2001; 103(5): 718-23.
[http://dx.doi.org/10.1161/01.CIR.103.5.718] [PMID: 11156884]
[129]
Léon C, Ravanat C, Freund M, Cazenave JP, Gachet C. Differential involvement of the P2Y1 and P2Y12 receptors in platelet procoagulant activity. Arterioscler Thromb Vasc Biol 2003; 23(10): 1941-7.
[http://dx.doi.org/10.1161/01.ATV.0000092127.16125.E6] [PMID: 12933533]
[130]
Hechler B, Nonne C, Roh EJ, et al. MRS2500 [2-iodo-N6-methyl-(N)-methanocarba-2′-deoxyadenosine-3′,5′-bisphosphate], a potent, selective, and stable antagonist of the platelet P2Y1 receptor with strong antithrombotic activity in mice. J Pharmacol Exp Ther 2006; 316(2): 556-63.
[http://dx.doi.org/10.1124/jpet.105.094037] [PMID: 16236815]
[131]
Wong PC, Watson C, Crain EJ. The P2Y1 receptor antagonist MRS2500 prevents carotid artery thrombosis in cynomolgus monkeys. J Thromb Thrombolysis 2016; 41(3): 514-21.
[http://dx.doi.org/10.1007/s11239-015-1302-7] [PMID: 26660522]
[132]
Yanachkov IB, Chang H, Yanachkova MI, et al. New highly active antiplatelet agents with dual specificity for platelet P2Y1 and P2Y12 adenosine diphosphate receptors. Eur J Med Chem 2016; 107: 204-18.
[http://dx.doi.org/10.1016/j.ejmech.2015.10.055] [PMID: 26588064]
[133]
Abdulqawi R, Dockry R, Holt K, et al. P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study. Lancet 2015; 385(9974): 1198-205.
[http://dx.doi.org/10.1016/S0140-6736(14)61255-1] [PMID: 25467586]
[134]
Keystone EC, Wang MM, Layton M, Hollis S, McInnes IB. Clinical evaluation of the efficacy of the P2X7 purinergic receptor antagonist AZD9056 on the signs and symptoms of rheumatoid arthritis in patients with active disease despite treatment with methotrexate or sulphasalazine. Ann Rheum Dis 2012; 71(10): 1630-5.
[http://dx.doi.org/10.1136/annrheumdis-2011-143578] [PMID: 22966146]
[135]
Stock TC, Bloom BJ, Wei N, et al. 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 2012; 39(4): 720-7.
[http://dx.doi.org/10.3899/jrheum. 110874] [PMID: 22382341]
[136]
Welsh RC, Rao SV, Zeymer U, et al. A randomized, double-blind, active-controlled phase 2 trial to evaluate a novel selective and reversible intravenous and oral P2Y12 inhibitor elinogrel versus clopidogrel in patients undergoing nonurgent percutaneous coronary intervention: The INNOVATE-PCI trial. Circ Cardiovasc Interv 2012; 5(3): 336-46.
[http://dx.doi.org/10.1161/CIRCINTER VENTIONS.111.964197] [PMID: 22647518]
[137]
Tam CC, Kwok J, Wong A, et al. Genotyping-guided approach versus the conventional approach in selection of oral P2Y12 receptor blockers in Chinese patients suffering from acute coronary syndrome. J Int Med Res 2017; 45(1): 134-46.
[http://dx.doi.org/ 10.1177/0300060516677190] [PMID: 28222641]
[138]
Spiel AO, Derhaschnig U, Schwameis M, Bartko J, Siller-Matula JM, Jilma B. Effects of prasugrel on platelet inhibition during systemic endotoxaemia: a randomized controlled trial. Clin Sci (Lond) 2012; 123(10): 591-600.
[http://dx.doi.org/10.1042/CS20120194] [PMID: 22646240]
[139]
Patti G, Polacco M, Taurino E, Gaudio C, Greco C. Effects of cigarette smoking on platelet reactivity during P2Y12 inhibition in patients with myocardial infarction undergoing drug-eluting stent implantation: results from the prospective cigarette smoking on platelet reactivity (COPTER) study. J Thromb Thrombolysis 2016; 41(4): 648-53.
[http://dx.doi.org/10.1007/s11239-016-1341-8] [PMID: 26849144]
[140]
Hobl EL, Stimpfl T, Ebner J, et al. Morphine decreases clopidogrel concentrations and effects: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol 2014; 63(7): 630-5.
[http://dx.doi.org/10.1016/j.jacc.2013.10.068] [PMID: 24315907]
[141]
Hobl EL, Reiter B, Schoergenhofer C, et al. Morphine interaction with prasugrel: a double-blind, cross-over trial in healthy volunteers. Clin Res Cardiol 2016; 105(4): 349-55.
[http://dx.doi.org/ 10.1007/s00392-015-0927-z] [PMID: 26493304]
[142]
Berger JS, Roe MT, Gibson CM, et al. Safety and feasibility of adjunctive antiplatelet therapy with intravenous elinogrel, a direct-acting and reversible P2Y12 ADP-receptor antagonist, before primary percutaneous intervention in patients with ST-elevation myocardial infarction: the Early Rapid ReversAl of platelet thromboSis with intravenous Elinogrel before PCI to optimize reperfusion in acute Myocardial Infarction (ERASE MI) pilot trial. Am Heart J 2009; 158(6): 998-1004.e1.
[http://dx.doi.org/10.1016/j.ahj. 2009.10.010] [PMID: 19958867]
[143]
Dudek D, Widimsky P, Bolognese L, Goldstein P, Hamm C, Tanguay J-F, et al. Impact of prasugrel pretreatment and timing of coronary artery bypass grafting on clinical outcomes of patients with non-st-segment elevation myocardial infarction: from the accoast study. Circulation 2014; 130(5): 1025-1032.e2.
[PMID: 26542513]
[144]
Montalescot G, Collet JP, Ecollan P, et al. Effect of prasugrel pre-treatment strategy in patients undergoing percutaneous coronary intervention for NSTEMI: the ACCOAST-PCI study. J Am Coll Cardiol 2014; 64(24): 2563-71.
[http://dx.doi.org/10.1016/j.jacc.2014.08.053] [PMID: 25524333]
[145]
Montalescot G, Bolognese L, Dudek D, et al. Pretreatment with prasugrel in non-ST-segment elevation acute coronary syndromes. N Engl J Med 2013; 369(11): 999-1010.
[http://dx.doi.org/10.1056/NEJMoa1308075] [PMID: 23991622]
[146]
Ariotti S, Ortega-Paz L, van Leeuwen M, et al. Effects of ticagrelor, prasugrel, or clopidogrel on endothelial function and other vascular biomarkers. JACC Cardiovasc Interv 2018; 11(16): 1576-86.
[http://dx.doi.org/10.1016/j.jcin.2018.04.022] [PMID: 29805112]
[147]
Kim JS, Han DC, Jeong YH, et al. Antiplatelet effect of ticagrelor compared to tirofiban in non-ST-segment elevation ACS patients undergoing PCI. The result of the TE-CLOT trial. Thromb Haemost 2016; 115(1): 213-21.
[http://dx.doi.org/10.1160/TH15-02-0180] [PMID: 26581884]
[148]
Valgimigli M, Tebaldi M, Campo G, et al. Prasugrel versus tirofiban bolus with or without short post-bolus infusion with or without concomitant prasugrel administration in patients with myocardial infarction undergoing coronary stenting: the FABOLUS PRO (Facilitation through Aggrastat By drOpping or shortening Infusion Line in patients with ST-segment elevation myocardial infarction compared to or on top of PRasugrel given at loading dOse) trial. JACC Cardiovasc Interv 2012; 5(3): 268-77.
[http://dx.doi.org/ 10.1016/j.jcin.2012.01.006] [PMID: 22440491]
[149]
Trenk D, Stone GW, Gawaz M, et al. A randomized trial of prasugrel versus clopidogrel in patients with high platelet reactivity on clopidogrel after elective percutaneous coronary intervention with implantation of drug-eluting stents: results of the TRIGGER-PCI (Testing Platelet Reactivity In Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel) study. J Am Coll Cardiol 2012; 59(24): 2159-64.
[http://dx.doi.org/10.1016/j.jacc.2012.02.026] [PMID: 22520250]
[150]
trials.gov/ct2/show/results/NCT01569438?term=af-219&phase= 123&rank=8§=X6430125#more
[151]
Eser A, Colombel J-F, Rutgeerts P, et al. Safety and efficacy of an oral inhibitor of the purinergic receptor P2X7 in adult patients with moderately to severely active Crohn’s disease: A randomized placebo-controlled, double-blind, phase IIa study. Inflamm Bowel Dis 2015; 21(10): 2247-53.
[http://dx.doi.org/10.1097/MIB. 0000000000000514] [PMID: 26197451]
[152]
Savi P, Herbert J-M. Clopidogrel and ticlopidine: P2Y12 adenosine diphosphate-receptor antagonists for the prevention of atherothrombosis. Semin Thromb Hemost 2005; 31(2): 174-83.
[http://dx.doi.org/10.1055/s-2005-869523] [PMID: 15852221]
[153]
Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345(7): 494-502.
[http://dx.doi.org/10.1056/NEJMoa010746] [PMID: 11519503]
[154]
Scott DM, Norwood RM, Parra D. P2Y12 inhibitors in cardiovascular disease: focus on prasugrel. Ann Pharmacother 2009; 43(1): 64-76.
[http://dx.doi.org/10.1345/aph.1G726] [PMID: 19050170]
[155]
Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357(20): 2001-15.
[http://dx.doi.org/10.1056/NEJMoa 0706482] [PMID: 17982182]
[156]
Anderson SD, Shah NK, Yim J, Epstein BJ. Efficacy and safety of ticagrelor: a reversible P2Y12 receptor antagonist. Ann Pharmacother 2010; 44(3): 524-37.
[http://dx.doi.org/10.1345/aph.1M548] [PMID: 20124464]
[157]
Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361(11): 1045-57.
[http://dx.doi.org/10.1056/NEJMoa0904 327] [PMID: 19717846]
[158]
Ueno M, Rao SV, Angiolillo DJ. Elinogrel: pharmacological principles, preclinical and early phase clinical testing. Future Cardiol 2010; 6(4): 445-53.
[http://dx.doi.org/10.2217/fca.10.67] [PMID: 20608816]
[159]
Oestreich JH. Elinogrel, a reversible P2Y12 receptor antagonist for the treatment of acute coronary syndrome and prevention of secondary thrombotic events. Curr Opin Investig Drugs 2010; 11(3): 340-8.
[PMID: 20178048]
[160]
Walsh JA III, Price MJ. Cangrelor for treatment of arterial thrombosis. Expert Opin Pharmacother 2014; 15(4): 565-72.
[http://dx.doi.org/10.1517/14656566.2014.882319] [PMID: 24479981]
[161]
Swartz TH, Dubyak GR, Chen BK. Purinergic receptors: Key mediators of HIV-1 infection and inflammation. Front Immunol 2015; 6: 585.
[http://dx.doi.org/10.3389/fimmu.2015.00585] [PMID: 26635799]
[162]
Burnstock G. Purinergic Mechanisms and Pain.Pharmacological Mechanisms and the Modulation of Pain 1st ed. 2016; 91-137.
[http://dx.doi.org/10.1016/bs.apha.2015.09.001]
[163]
Di Virgilio F, Adinolfi E. Extracellular purines, purinergic receptors and tumor growth. Oncogene 2017; 36(3): 293-303.
[http://dx.doi.org/10.1038/onc.2016.206] [PMID: 27321181]
[164]
Cekic C, Linden J. Purinergic regulation of the immune system. Nat Rev Immunol 2016; 16(3): 177-92.
[http://dx.doi.org/10.1038/nri.2016.4] [PMID: 26922909]
[165]
Fuller SJ, Stokes L, Skarratt KK, Gu BJ, Wiley JS. Genetics of the P2X7 receptor and human disease. Purinergic Signal 2009; 5(2): 257-62.
[http://dx.doi.org/10.1007/s11302-009-9136-4] [PMID: 19319666]
[166]
Sorge RE, Trang T, Dorfman R, et al. Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity. Nat Med 2012; 18(4): 595-9.
[http://dx.doi.org/10.1038/nm.2710] [PMID: 22447075]
[167]
Balunas MJ, Kinghorn AD. Drug discovery from medicinal plants. Life Sci 2005; 78(5): 431-41.
[http://dx.doi.org/10.1016/j.lfs.2005. 09.012] [PMID: 16198377]
[168]
Saklani A, Kutty SK. Plant-derived compounds in clinical trials. Drug Discov Today 2008; 13(3-4): 161-71.
[http://dx.doi.org/10. 1016/j.drudis.2007.10.010] [PMID: 18275914]
[169]
Galvez-Llompart M, Zanni R, García-Domenech R. Modeling natural anti-inflammatory compounds by molecular topology. Int J Mol Sci 2011; 12(12): 9481-503.
[http://dx.doi.org/10.3390/ijms12129481] [PMID: 22272145]