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CGS-21680

CGS-21680 is a specific adenosine A2A subtype receptor agonist. It is usually presented as an organic hydrochloride salt with a molecular weight of 536.0 g/M. It is soluble up to 3.4 mg/mL in DMSO and 20 mg/mL in 45% (w/v) aq 2-hydroxypropyl-β-cyclodextrin. The chemical is currently used by researchers interested in studying neuronal transmission with a high-affinity, subtype specific analogue for adenosine. This includes research in respiration where it is believed that A2A receptors are involved in rhythm generation in the pre-Bötzinger complex. The drug is not currently approved for use in a therapeutic capacity. (source: http://en.wikipedia.org/wiki/CGS-21680). 

Current developer:    Novartis.

1: Jones-Cage C, Stratford TR, Wirtshafter D. Differential effects of the adenosine A(2A) agonist CGS-21680 and haloperidol on food-reinforced fixed ratio responding in the rat. Psychopharmacology (Berl). 2011 Sep 7. [Epub ahead of print] PubMed PMID: 21898173.

2: Mazzon E, Esposito E, Impellizzeri D, DI Paola R, Melani A, Bramanti P, Pedata F, Cuzzocrea S. CGS 21680, an agonist of the adenosine (A2A) receptor, reduces progression of murine type II collagen-induced arthritis. J Rheumatol. 2011 Oct;38(10):2119-29. Epub 2011 Jul 15. PubMed PMID: 21765105.

3: Impellizzeri D, Di Paola R, Esposito E, Mazzon E, Paterniti I, Melani A, Bramanti P, Pedata F, Cuzzocrea S. CGS 21680, an agonist of the adenosine (A2A) receptor, decreases acute lung inflammation. Eur J Pharmacol. 2011 Oct 1;668(1-2):305-16. Epub 2011 Jul 8. PubMed PMID: 21756897.

4: Vuaden FC, Savio LE, Bastos CM, Bogo MR, Bonan CD. Adenosine A(2A) receptor agonist (CGS-21680) prevents endotoxin-induced effects on nucleotidase activities in mouse lymphocytes. Eur J Pharmacol. 2011 Jan 25;651(1-3):212-7. Epub 2010 Nov 27. PubMed PMID: 21114987.

5: Palma AG, Muchnik S, Losavio AS. Excitatory effect of the A2A adenosine receptor agonist CGS-21680 on spontaneous and K+-evoked acetylcholine release at the mouse neuromuscular junction. Neuroscience. 2011 Jan 13;172:164-76. Epub 2010 Nov 2. PubMed PMID: 20971164.

6: Ferrante A, Martire A, Armida M, Chiodi V, Pézzola A, Potenza RL, Domenici MR, Popoli P. Influence of CGS 21680, a selective adenosine A(2A) receptor agonist, on NMDA receptor function and expression in the brain of Huntington's disease mice. Brain Res. 2010 Apr 6;1323:184-91. Epub 2010 Feb 4. PubMed PMID: 20138162.

7: Genovese T, Melani A, Esposito E, Mazzon E, Di Paola R, Bramanti P, Pedata F, Cuzzocrea S. The selective adenosine A2A receptor agonist CGS 21680 reduces JNK MAPK activation in oligodendrocytes in injured spinal cord. Shock. 2009 Dec;32(6):578-85. PubMed PMID: 19295488.

8: Font L, Mingote S, Farrar AM, Pereira M, Worden L, Stopper C, Port RG, Salamone JD. Intra-accumbens injections of the adenosine A2A agonist CGS 21680 affect effort-related choice behavior in rats. Psychopharmacology (Berl). 2008 Sep;199(4):515-26. Epub 2008 May 20. PubMed PMID: 18491078; PubMed Central PMCID: PMC2643064.

9: Mingote S, Pereira M, Farrar AM, McLaughlin PJ, Salamone JD. Systemic administration of the adenosine A(2A) agonist CGS 21680 induces sedation at doses that suppress lever pressing and food intake. Pharmacol Biochem Behav. 2008 May;89(3):345-51. Epub 2008 Jan 17. PubMed PMID: 18281083; PubMed Central PMCID: PMC2674372.

10: Selmeczy Z, Csóka B, Pacher P, Vizi ES, Haskó G. The adenosine A2A receptor agonist CGS 21680 fails to ameliorate the course of dextran sulphate-induced colitis in mice. Inflamm Res. 2007 May;56(5):204-9. PubMed PMID: 17588136; PubMed Central PMCID: PMC2225471.

11: Lin CL, Shih HC, Lieu AS, Lee KS, Dumont AS, Kassell NF, Howng SL, Kwan AL. Attenuation of experimental subarachnoid hemorrhage--induced cerebral vasospasm by the adenosine A2A receptor agonist CGS 21680. J Neurosurg. 2007 Mar;106(3):436-41. PubMed PMID: 17367066.

12: Cabeza de Vaca S, Kannan P, Pan Y, Jiang N, Sun Y, Carr KD. The adenosine A2A receptor agonist, CGS-21680, blocks excessive rearing, acquisition of wheel running, and increases nucleus accumbens CREB phosphorylation in chronically food-restricted rats. Brain Res. 2007 Apr 20;1142:100-9. Epub 2007 Jan 17. PubMed PMID: 17292868; PubMed Central PMCID: PMC1868560.

13: Halldner L, Lopes LV, Daré E, Lindström K, Johansson B, Ledent C, Cunha RA, Fredholm BB. Binding of adenosine receptor ligands to brain of adenosine receptor knock-out mice: evidence that CGS 21680 binds to A1 receptors in hippocampus. Naunyn Schmiedebergs Arch Pharmacol. 2004 Oct;370(4):270-8. Epub 2004 Sep 18. PubMed PMID: 15378230.

14: Agnati LF, Leo G, Vergoni AV, Martínez E, Hockemeyer J, Lluis C, Franco R, Fuxe K, Ferré S. Neuroprotective effect of L-DOPA co-administered with the adenosine A2A receptor agonist CGS 21680 in an animal model of Parkinson's disease. Brain Res Bull. 2004 Aug 30;64(2):155-64. PubMed PMID: 15342103.

15: Lopes LV, Halldner L, Rebola N, Johansson B, Ledent C, Chen JF, Fredholm BB, Cunha RA. Binding of the prototypical adenosine A(2A) receptor agonist CGS 21680 to the cerebral cortex of adenosine A(1) and A(2A) receptor knockout mice. Br J Pharmacol. 2004 Mar;141(6):1006-14. Epub 2004 Mar 1. PubMed PMID: 14993095; PubMed Central PMCID: PMC1574266.

16: Schindler CW, Karcz-Kubicha M, Thorndike EB, Müller CE, Tella SR, Goldberg SR, Ferré S. Lack of adenosine A1 and dopamine D2 receptor-mediated modulation of the cardiovascular effects of the adenosine A2A receptor agonist CGS 21680. Eur J Pharmacol. 2004 Jan 26;484(2-3):269-75. PubMed PMID: 14744613.

17: Wardas J, Konieczny J, Pietraszek M. Influence of CGS 21680, a selective adenosine A(2A) agonist, on the phencyclidine-induced sensorimotor gating deficit and motor behaviour in rats. Psychopharmacology (Berl). 2003 Jul;168(3):299-306. Epub 2003 Apr 9. PubMed PMID: 12684736.

18: Andersen MB, Fuxe K, Werge T, Gerlach J. The adenosine A2A receptor agonist CGS 21680 exhibits antipsychotic-like activity in Cebus apella monkeys. Behav Pharmacol. 2002 Dec;13(8):639-44. PubMed PMID: 12478214.

19: Fozard JR, Ellis KM, Villela Dantas MF, Tigani B, Mazzoni L. Effects of CGS 21680, a selective adenosine A2A receptor agonist, on allergic airways inflammation in the rat. Eur J Pharmacol. 2002 Mar 8;438(3):183-8. PubMed PMID: 11909610.

20: Sills TL, Azampanah A, Fletcher PJ. The adenosine A2A agonist CGS 21680 reverses the reduction in prepulse inhibition of the acoustic startle response induced by phencyclidine, but not by apomorphine and amphetamine. Psychopharmacology (Berl). 2001 Jul;156(2-3):187-93. PubMed PMID: 11549222.

21: Knapp CM, Foye MM, Cottam N, Ciraulo DA, Kornetsky C. Adenosine agonists CGS 21680 and NECA inhibit the initiation of cocaine self-administration. Pharmacol Biochem Behav. 2001 Apr;68(4):797-803. PubMed PMID: 11526979.

22: Díaz-Cabiale Z, Hurd Y, Guidolin D, Finnman UB, Zoli M, Agnati LF, Vanderhaeghen JJ, Fuxe K, Ferré S. Adenosine A2A agonist CGS 21680 decreases the affinity of dopamine D2 receptors for dopamine in human striatum. Neuroreport. 2001 Jul 3;12(9):1831-4. PubMed PMID: 11435907.

23: Lasley RD, Jahania MS, Mentzer RM Jr. Beneficial effects of adenosine A(2a) agonist CGS-21680 in infarcted and stunned porcine myocardium. Am J Physiol Heart Circ Physiol. 2001 Apr;280(4):H1660-6. PubMed PMID: 11247777.

24: Ramafi G, Anderson R, Theron AJ, Feldman C, Taylor GW, Wilson R, Cole PJ. CGS 21680, dibutyryl cyclic AMP and rolipram attenuate the pro-inflammatory interactions of the Pseudomonas aeruginosa -derived pigment, 1-hydroxyphenazine, with human neutrophils. Pulm Pharmacol Ther. 2000;13(6):293-9. PubMed PMID: 11061984.

25: Richter A, Hamann M, Bartling C. CGS 21680 exerts marked antidystonic effects in a genetic model of paroxysmal dyskinesia. Eur J Pharmacol. 2000 Sep 22;404(3):299-302. PubMed PMID: 10996595.

26: Visser SS, Theron AJ, Ramafi G, Ker JA, Anderson R. Apparent involvement of the A(2A) subtype adenosine receptor in the anti-inflammatory interactions of CGS 21680, cyclopentyladenosine, and IB-MECA with human neutrophils. Biochem Pharmacol. 2000 Oct 1;60(7):993-9. PubMed PMID: 10974209.

27: Apasov SG, Chen JF, Smith PT, Schwarzschild MA, Fink JS, Sitkovsky MV. Study of A(2A) adenosine receptor gene deficient mice reveals that adenosine analogue CGS 21680 possesses no A(2A) receptor-unrelated lymphotoxicity. Br J Pharmacol. 2000 Sep;131(1):43-50. PubMed PMID: 10960067; PubMed Central PMCID: PMC1572291.

28: El Yacoubi M, Ledent C, Parmentier M, Costentin J, Vaugeois J. SCH 58261 and ZM 241385 differentially prevent the motor effects of CGS 21680 in mice: evidence for a functional 'atypical' adenosine A(2A) receptor. Eur J Pharmacol. 2000 Jul 28;401(1):63-77. PubMed PMID: 10915839.

29: He ZX, Cwajg E, Hwang W, Hartley CJ, Funk E, Michael LH, Verani MS. Myocardial blood flow and myocardial uptake of (201)Tl and (99m)Tc-sestamibi during coronary vasodilation induced by CGS-21680, a selective adenosine A(2A) receptor agonist. Circulation. 2000 Jul 25;102(4):438-44. PubMed PMID: 10908217.

30: Anderson R, Visser SS, Ramafi G, Theron AJ. Accelerated resequestration of cytosolic calcium and suppression of the pro-inflammatory activities of human neutrophils by CGS 21680 in vitro. Br J Pharmacol. 2000 Jun;130(4):717-24. PubMed PMID: 10864876; PubMed Central PMCID: PMC1572119.

31: Cunha RA, Constantino MD, Ribeiro JA. G protein coupling of CGS 21680 binding sites in the rat hippocampus and cortex is different from that of adenosine A1 and striatal A2A receptors. Naunyn Schmiedebergs Arch Pharmacol. 1999 Apr;359(4):295-302. PubMed PMID: 10344528.

32: Nekooeian AA, Tabrizchi R. Haemodynamic effects of a selective adenosine A2A receptor agonist, CGS 21680, in chronic heart failure in anaesthetized rats. Br J Pharmacol. 1998 Oct;125(4):651-8. PubMed PMID: 9831898; PubMed Central PMCID: PMC1571031.

33: Phillis JW. Inhibitory action of CGS 21680 on cerebral cortical neurons is antagonized by bicuculline and picrotoxin-is GABA involved? Brain Res. 1998 Oct 5;807(1-2):193-8. PubMed PMID: 9757034.

34: Nekooeian AA, Tabrizchi R. Effects of CGS 21680, a selective A2A adenosine receptor agonist, on cardiac output and vascular resistance in acute heart failure in the anaesthetized rat. Br J Pharmacol. 1998 Apr;123(8):1666-72. PubMed PMID: 9605574; PubMed Central PMCID: PMC1565321.

35: Lindström K, Ongini E, Fredholm BB. The selective adenosine A2A receptor antagonist SCH 58261 discriminates between two different binding sites for [3H]-CGS 21680 in the rat brain. Naunyn Schmiedebergs Arch Pharmacol. 1996 Oct;354(4):539-41. PubMed PMID: 8897460.

36: Barraco RA, Helfman CC, Anderson GF. Augmented release of serotonin by adenosine A2a receptor activation and desensitization by CGS 21680 in the rat nucleus tractus solitarius. Brain Res. 1996 Sep 16;733(2):155-61. PubMed PMID: 8891297.

37: Nekooeian AA, Tabrizchi R. Effects of adenosine A2A receptor agonist, CGS 21680, on blood pressure, cardiac index and arterial conductance in anaesthetized rats. Eur J Pharmacol. 1996 Jun 27;307(2):163-9. PubMed PMID: 8832218.

38: Varani K, Gessi S, Dalpiaz A, Borea PA. Pharmacological and biochemical characterization of purified A2a adenosine receptors in human platelet membranes by [3H]-CGS 21680 binding. Br J Pharmacol. 1996 Apr;117(8):1693-701. PubMed PMID: 8732278; PubMed Central PMCID: PMC1909568.

39: Cunha RA, Johansson B, Constantino MD, Sebastião AM, Fredholm BB. Evidence for high-affinity binding sites for the adenosine A2A receptor agonist [3H] CGS 21680 in the rat hippocampus and cerebral cortex that are different from striatal A2A receptors. Naunyn Schmiedebergs Arch Pharmacol. 1996 Feb;353(3):261-71. PubMed PMID: 8692280.

40: Hiley CR, Bottrill FE, Warnock J, Richardson PJ. Effects of pH on responses to adenosine, CGS 21680, carbachol and nitroprusside in the isolated perfused superior mesenteric arterial bed of the rat. Br J Pharmacol. 1995 Nov;116(6):2641-6. PubMed PMID: 8590983; PubMed Central PMCID: PMC1909135.

41: Hillefors-Berglund M, Hedlund PB, von Euler G. Effects of CGS 21680 in vivo on dopamine D2 agonist binding in the rat brain. Brain Res. 1995 Aug 28;690(1):34-40. PubMed PMID: 7496804.

42: Johansson B, Fredholm BB. Further characterization of the binding of the adenosine receptor agonist [3H]CGS 21680 to rat brain using autoradiography. Neuropharmacology. 1995 Apr;34(4):393-403. PubMed PMID: 7566470.

43: Kirk IP, Richardson PJ. Further characterization of [3H]-CGS 21680 binding sites in the rat striatum and cortex. Br J Pharmacol. 1995 Jan;114(2):537-43. PubMed PMID: 7881753; PubMed Central PMCID: PMC1510262.

44: Varani K, Borea PA, Guerra L, Dionisotti S, Zocchi C, Ongini E. Binding characteristics of the adenosine A2 receptor ligand [3H]CGS 21680 to human platelet membranes. Biochem Pharmacol. 1994 Oct 18;48(8):1658-61. PubMed PMID: 7980632.

45: Irth H, Cleton A, Mathôt RA, Danhof M, IJzerman AP, Tjaden UR, van der Greef J. Liquid chromatographic determination of the adenosine receptor agonist CGS 21680 in blood using on-line solid-phase extraction on a phenylboronic acid support and fluorescence detection. J Chromatogr B Biomed Appl. 1994 Aug 5;658(1):207-12. PubMed PMID: 7952127.

46: Popoli P, Pèzzola A, Reggio R, Caporali MG, Scotti de Carolis A. CGS 21680 antagonizes motor hyperactivity in a rat model of Huntington's disease. Eur J Pharmacol. 1994 May 12;257(1-2):R5-6. PubMed PMID: 8082686.

47: Johansson B, Georgiev V, Parkinson FE, Fredholm BB. The binding of the adenosine A2 receptor selective agonist [3H]CGS 21680 to rat cortex differs from its binding to rat striatum. Eur J Pharmacol. 1993 Oct 15;247(2):103-10. PubMed PMID: 8281998.

48: Janusz CA, Berman RF. Adenosinergic modulation of the EEG and locomotor effects of the A2 agonist, CGS 21680. Pharmacol Biochem Behav. 1993 Aug;45(4):913-9. PubMed PMID: 8415830.

49: James S, Richardson PJ. The subcellular distribution of [3H]-CGS 21680 binding sites in the rat striatum: copurification with cholinergic nerve terminals. Neurochem Int. 1993 Aug;23(2):115-22. PubMed PMID: 8369737.

50: Broad RM, Cook MA. Inhibition of neurotransmitter release from enteric nerve endings by 2-[p-(carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamido-adenosine (CGS-21680) and related adenosine analogs: lack of simple competition by antagonists. J Pharmacol Exp Ther. 1993 Aug;266(2):634-41. PubMed PMID: 8102645.

51: Johansson B, Parkinson FE, Fredholm BB. Effects of mono- and divalent ions on the binding of the adenosine analogue CGS 21680 to adenosine A2 receptors in rat striatum. Biochem Pharmacol. 1992 Dec 15;44(12):2365-70. PubMed PMID: 1472101.

52: Makujina SR, Sabouni MH, Bhatia S, Douglas FL, Mustafa SJ. Vasodilatory effects of adenosine A2 receptor agonists CGS 21680 and CGS 22492 in human vasculature. Eur J Pharmacol. 1992 Oct 20;221(2-3):243-7. PubMed PMID: 1426003.

53: Janusz CA, Berman RF. The A2-selective adenosine analog, CGS 21680, depresses locomotor activity but does not block amygdala kindled seizures in rats. Neurosci Lett. 1992 Jul 20;141(2):247-50. PubMed PMID: 1436642.

54: Chovan JP, Zane PA, Greenberg GE. Automated-extraction, high-performance liquid chromatographic method and pharmacokinetics in rats of a highly A2-selective adenosine agonist, CGS 21680. J Chromatogr. 1992 Jul 1;578(1):77-83. PubMed PMID: 1400789.

55: O'Regan MH, Simpson RE, Perkins LM, Phillis JW. The selective A2 adenosine receptor agonist CGS 21680 enhances excitatory transmitter amino acid release from the ischemic rat cerebral cortex. Neurosci Lett. 1992 Apr 13;138(1):169-72. PubMed PMID: 1357597.

56: Balwierczak JL, Sharif R, Krulan CM, Field FP, Weiss GB, Miller MJ. Comparative effects of a selective adenosine A2 receptor agonist, CGS 21680, and nitroprusside in vascular smooth muscle. Eur J Pharmacol. 1991 Apr 17;196(2):117-23. PubMed PMID: 1678715.

57: Wan W, Sutherland GR, Geiger JD. Binding of the adenosine A2 receptor ligand [3H]CGS 21680 to human and rat brain: evidence for multiple affinity sites. J Neurochem. 1990 Nov;55(5):1763-71. PubMed PMID: 2213023.

58: Parkinson FE, Fredholm BB. Autoradiographic evidence for G-protein coupled A2-receptors in rat neostriatum using [3H]-CGS 21680 as a ligand. Naunyn Schmiedebergs Arch Pharmacol. 1990 Jul;342(1):85-9. PubMed PMID: 1698265.

59: Lupica CR, Cass WA, Zahniser NR, Dunwiddie TV. Effects of the selective adenosine A2 receptor agonist CGS 21680 on in vitro electrophysiology, cAMP formation and dopamine release in rat hippocampus and striatum. J Pharmacol Exp Ther. 1990 Mar;252(3):1134-41. PubMed PMID: 2156991.

60: Phillis JW. The selective adenosine A2 receptor agonist, CGS 21680, is a potent depressant of cerebral cortical neuronal activity. Brain Res. 1990 Feb 19;509(2):328-30. PubMed PMID: 2322828.

61: Jarvis MF, Schulz R, Hutchison AJ, Do UH, Sills MA, Williams M. [3H]CGS 21680, a selective A2 adenosine receptor agonist directly labels A2 receptors in rat brain. J Pharmacol Exp Ther. 1989 Dec;251(3):888-93. PubMed PMID: 2600819.

62: Jarvis MF, Williams M. Direct autoradiographic localization of adenosine A2 receptors in the rat brain using the A2-selective agonist, [3H]CGS 21680. Eur J Pharmacol. 1989 Sep 13;168(2):243-6. PubMed PMID: 2558026.