Ticagrelor Inhibits Adenosine Uptake In Vitro and Enhances Adenosine-Mediated Hyperemia Responses in a Canine Model

Journal of Cardiovascular Pharmacology and Therapeutics

Volumn 17, Issue 2, 2012, Pages 164-172

  Van Giezen, J J J ^a   Sidaway, James ^b   Glaves, Philip ^b   Kirk, Ian ^b   Björkman, Jan Arne ^a  

^a ASTRAZENECA R AND D   (Sweden)

^b ASTRAZENECA   (United Kingdom)

Author keywords

adenosine; animal model; dipyridamole; hyperemia; ticagrelor

Indexed keywords

ADENOSINE; DIPYRIDAMOLE; DRUG DERIVATIVE; PURINERGIC P2Y RECEPTOR ANTAGONIST; TICAGRELOR;

ACUTE CORONARY SYNDROME; ANIMAL; ARTICLE; CELL LINE; COMPARATIVE STUDY; CORONARY ARTERY BLOOD FLOW; DISEASE MODEL; DOG; DOSE RESPONSE; DRUG EFFECT; ERYTHROCYTE; FEMALE; HUMAN; HYPEREMIA; MALE; METABOLISM; PATHOPHYSIOLOGY; RAT; TUMOR CELL LINE;

ACUTE CORONARY SYNDROME; ADENOSINE; ANIMALS; CELL LINE; CELL LINE, TUMOR; CORONARY CIRCULATION; DIPYRIDAMOLE; DISEASE MODELS, ANIMAL; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; ERYTHROCYTES; FEMALE; HUMANS; HYPEREMIA; MALE; PURINERGIC P2Y RECEPTOR ANTAGONISTS; RATS;

EID: 84866479608     PISSN: 10742484     EISSN: 19404034     Source Type: Journal    
DOI: 10.1177/1074248411410883     Document Type: Article

References (44)

1. van Giezen JJ Humphries RG. Preclinical and clinical studies with selective reversible direct P2Y12 antagonists. Semin Thromb Hemost. 2005; 31(2):195-204.
2. van Giezen JJ Tomlinson W Berntsson P, et al. AZD6140 (ticagrelor) binds to the human P2Y12 receptor independently from ADP, but antagonizes ADP-induced receptor signaling and platelet aggregation. J Thromb Haemost. 2009; 7(9):1556-1565.
3. Husted S van Giezen JJ. Ticagrelor: the first reversibly binding oral P2Y12 receptor antagonist. Cardiovasc Ther. 2009; 27(4):259-274.
4. Husted S Emanuelsson H Heptinstall S Sandset PM Wickens M Peters G. Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: a double-blind comparison to clopidogrel with aspirin. Eur Heart J. 2006; 27(9):1038-1047.
5. Cannon CP Husted S Harrington RA, et al. Safety, tolerability, and initial efficacy of AZD6140, the first reversible oral adenosine diphosphate receptor antagonist, compared with clopidogrel, in patients with non-ST-segment elevation acute coronary syndrome: primary results of the DISPERSE-2 trial. J Am Coll Cardiol. 2007; 50(19):1844-1851. Correction in J Am Coll Cardiol. 2007;50:2196
6. Storey RF Husted S Harrington RA, et al. Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes. J Am Coll Cardiol. 2007; 50(19):1852-1856.
7. Wallentin L Becker RC Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009; 361(11):1045-1057.
8. Wiviott SD Braunwald E McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007; 357(20):2001-2015.
9. Michelson AD Frelinger AL 3rd Braunwald E, et al. Pharmacodynamic assessment of platelet inhibition by prasugrel vs clopidogrel in the TRITON-TIMI 38 trial. Eur Heart J. 2009; 30(14):1753-1763.
10. Vijayalakshmi K Whittaker VJ Kunadian B, et al. Prospective, randomised, controlled trial to study the effect of intracoronary injection of verapamil and adenosine on coronary blood flow during percutaneous coronary intervention in patients with acute coronary syndromes. Heart. 2006; 92(9):1278-1284.
11. Marzilli M Orsini E Marraccini P Testa R. Beneficial effects of intracoronary adenosine as an adjunct to primary angioplasty in acute myocardial infarction. Circulation. 2000; 101(18):2154-2159.
12. Ross AM Gibbons RJ Stone GW Kloner RA Alexander RW. A randomized, double-blind, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II). J Am Coll Cardiol. 2005; 45(11):1775-1780.
13. Kloner RA Forman MB Gibbons RJ Ross AM Alexander RW Stone GW. Impact of time to therapy and reperfusion modality on the efficacy of adenosine in acute myocardial infarction: the AMISTAD-2 trial. Eur Heart J. 2006; 27(20):2400-2405.
14. Burki NK Dale WJ Lee LY. Intravenous adenosine and dyspnea in humans. J Appl Physiol. 2005; 98(1):180-185.
15. AstraZeneca R&D Mölndal data on file, study number 26709, experiment number 26709033.
16. AstraZeneca data on file, document SC-103269.
17. Baldwin SA Beal PR Yao SY King AE Cass CE Young JD. The equilibrative nucleoside transporter family, SLC29. Pflugers Arch. 2004; 447(5):735-743.
18. Gray JH Owen RP Giacomini KM. The concentrative nucleoside transporter family, SLC28. Pflugers Arch. 2004; 447(5):728-734.
19. Hammond JR Stolk M Archer RG McConnell K. Pharmacological analysis and molecular cloning of the canine equilibrative nucleoside transporter 1. Eur J Pharmcol. 2004; 491(1):9-19.
20. Rose JB Naydenova Z Bang A, et al. Equilibrative nucleoside transporter 1 plays an essential role in cardioprotection. Am J Physiol Heart Circ Physiol. 2010; 298(3):H771-H777.
21. Chaudary N Naydenova Z Shuralyova I Coe IR. Hypoxia regulates the adenosine transporter, mENT1, in the murine cardiomyocyte cell line, HL-1. Cardiovasc Res. 2004; 61(4):780-788.
22. Belardinelli L Shryock JC Snowdy S, et al. The A2A adenosine receptor mediates coronary vasodilation. J Pharmacol Exp Ther. 1998; 284(3):1066-1073.
23. Feoktistov I Ryzhov S Zhong H, et al. Hypoxia modulates adenosine receptors in human endothelial and smooth muscle cells toward an A2B angiogenic phenotype. Hypertension. 2004; 44(5):649-654.
24. Fredholm BB Ijzerman AP Jacobson KA Klotz KN, Linden J. International Union of Pharmacology, XXV: nomenclature and classification of adenosine receptors. Pharmacol Rev. 2001; 53(4):527-552.
25. Husted S Nedergaard OA. Inhibition of adrenergic neuroeffector transmission in rabbit pulmonary artery and aorta by adenosine and adenine nucleotides. Acta Pharmacol Toxicol. Copenh). 1981; 49(5):334-353.
26. Berne RM. The role of adenosine in the regulation of coronary blood flow. Circ Res. 1980; 47(6):807-813.
27. Mustafa SJ Morrison RR Teng B Pelleg A. Adenosine receptors and the heart: role in regulation of coronary blood flow and cardiac electrophysiology. Handb Exp Pharmacol. 2009; 193: 161-188.
28. Gresele P Arnout J Deckmyn H Vermylen J. Mechanism of the antiplatelet action of dipyridamole in whole blood: modulation of adenosine concentration and activity. Thromb Haemost. 1986; 55(1):12-18.
29. AstraZeneca, data on file, study report numbers SC-103208, SC-103260, SC-103370, 0355SY, and 1805KV.
30. Wilson RF Wyche K Christensen BV Zimmer S Laxson DD. Effects of adenosine on human coronary arterial circulation. Circulation. 1990; 82(5):1595-1606.
31. Wang K Zhou X Huang Y, et al. Adjunctive infusion of AZD6140, but not clopidogrel, with t-PA enables sustained coronary artery recanalization with recovery of myocardium perfusion in a canine model of myocardial infarction. Thromb Haemostas. 2010; 104(3):609-617.
32. Held C Åsenblad N Bassand JP, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes undergoing coronary artery bypass surgery. Results from the PLATO (Platelet Inhibition and Patient Outcomes) Trial. J Am Coll Cardiol. 2011; 57(6):672-684.
33. Montalescot G Wiviott SD Braunwald E, et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet. 2009; 373(9665):723-731.
34. Rankin AC Brooks R Ruskin JN McGovern BA. Adenosine and the treatment of supraventricular tachycardia. Am J Med. 1992; 92(6):655-664.
35. Balan KK Critchley M. Is the dyspnea during adenosine cardiac stress test caused by bronchospasm?. Am Heart J. 2001; 142(1):142-145.
36. Hong JL Ho CY Kwong K Lee LY. Activation of pulmonary C fibres by adenosine in anaesthetized rats: role of adenosine A1 receptors. J Physiol. 1998; 508(pt 1):109-118.
37. Diener HC Sacco RL Yusuf S, et al. Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study. Lancet Neurol. 2008; 7(10):875-884.
38. Sacco RL Diener HC Yusuf S, et al. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med. 2008; 359(12):1238-1251.
39. Beller GA. Pharmacologic stress imaging. JAMA. 1991; 265(5):633-638.
40. Ranhosky A Kempthorne-Rawson J. The safety of intravenous dipyridamole thallium myocardial perfusion imaging. Intravenous Dipyridamole Thallium Imaging Study Group. Circulation. 1990; 81(4):1205-1209.
41. Perper EJ Segall GM. Safety of dipyridamole-thallium imaging in high risk patients with known or suspected coronary artery disease. J Nucl Med. 1991; 32(11):2107-2114.
42. Aggrenox [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2009.
43. Harrington RA Stone GW McNulty S, et al. Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med. 2009; 361(24):2318-2329.
44. Bhatt DL Lincoff AM Gibson CM, et al. Intravenous platelet blockade with cangrelor during PCI. N Engl J Med. 2009; 361(24):2330-2341.