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Chemical Compound Review

CHEMBL331372     3-[4-[2-[[6-amino-9- [(2R,3R,4S,5S)-5...

Synonyms: SureCN724684, CHEBI:73283, CGS-21680, CS-0424, CHEBI:292029, ...
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Disease relevance of CGS21680

  • While activation of the A2a receptor by 1 microM CGS21680 could not mimic preconditioning, its stimulation during preconditioning hypoxia, however, attenuated the protection against hypoxia-induced injury [1].
  • In the cells treated with CGS21680, PI3K activation was prevented either by inhibiting adenylate cyclase and PKA with, respectively, 2,5-dideoxyadenosine and H89 or by blocking Galphai-protein and Src tyrosine kinase with, respectively, pertussis toxin and PP2 [2].
  • The increments produced by the infusion of CGS21680 at 0.2 and 2.0 pmol/min were totally diminished when the rats had been pretreated with an i.p. injection of (E)-1,3-dipropyl-7-methyl-8-(3,4-dimethoxystyryl)xanthine (KF17837; 30 mg/kg of body weight), a selective A2-adenosine antagonist [3].
  • Binding assays and assays of activation of adenylate cyclase with the agonists 5'-N-ethylcarboxyamidoadenosine (NECA) and CGS21680 have been used to compare adenosine receptors in rat pheochromocytoma PC12 cells and in rat striatum [4].
  • Injection of [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin immediately before prostaglandin E2 or CGS21680 significantly attenuated the hyperalgesia subsequently induced by these agents, i.e. the sensitivity to these hyperalgesic agents was decreased [5].

Psychiatry related information on CGS21680


High impact information on CGS21680

  • NECA 10 microM evoked IL-8 release from HMC-1, but CGS21680 10 microM had no effect [9].
  • Essentially the same effects of CGS21680 and CHA were observed when these compounds were administered to the parenchymal region of the rostral basal forebrain through chronically implanted microdialysis probes [3].
  • Tc1 and Tc2 cells had similar adenosine signaling, as measured by intracellular cyclic AMP (cAMP) increase upon adenosine A(2A) receptor agonism by CGS21680 (CGS) [10].
  • Furthermore, inhibition by CGS21680 of fMLP-induced PLD activity was reversed by CSC or CGS15943 [11].
  • Moreover, the membrane translocation of both PKCalpha, RhoA, and ARF in response to fMLP was attenuated by CGS21680 and this effect of the A2a receptor agonist was antagonized by CSC or CGS15943 [11].

Chemical compound and disease context of CGS21680

  • In the pertussis toxin-treated myocyte, the maximal increases caused by the equipotent or A2-agonists (NECA, MECA, CV-1808, and CGS21680, from 49.6 +/- 3% to 52.5 +/- 6%, n = 8-12) were significantly greater than those elicited by the A1-agonists (2-CADO, S-PIA, R-PIA, and DCCA, from 12 +/- 4% to 37 +/- 3%, n = 8) (p less than 0.05, by t test) [12].
  • Akt phosphorylation is not stimulated by 100 nM N6-cyclopentyladenosine (A1-selective) or CGS21680 (A2A-selective) and is absent in cells pretreated with wortmannin or pertussis toxin [13].
  • The A2A receptor agonist, CGS21680 (0.3-300 microg kg(-1), i.v.), and the A3 receptor agonist, IB-MECA (0.3-300 microg kg(-1), i.v.), each induced only a dose-dependent hypotension [14].
  • RESULTS: The ED50s of KW-6002 in the reversal of CGS21680-induced and reserpine-induced catalepsy were 0.05 mg/kg, PO and 0.26 mg/kg, PO, respectively [15].
  • Under conditions of A1 receptor blockade, pretreatment with DU24565 or fluoxetine, enhanced the stimulatory effects of CGS21680 and PD125944 as well as inhibitory effects of DMPX on 5-HT level, whereas the inhibitory effect of APNEA was abolished [16].

Biological context of CGS21680

  • Consistently, an increased phosphorylation of p38 MAPK was observed in preconditioned or CGS21680-treated hepatocytes, and this effect was abolished by PKC-blocker, chelerythrine [17].
  • The adenylyl cyclase-protein kinase A cascade has no role in the down-regulation of VEGF mRNA induced by the A(2A)AR agonist, 2-[4-[(2-carboxyethyl)phenyl]ethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680) [18].
  • This high affinity site is substantiated by the finding that the IC50 of CGS21680 in competition with 125I-APE binding to striatal membranes is shifted leftward in membranes diluted for 4 min before filtration, to selectively dissociate radioligand from low affinity receptors [19].
  • The A(2A)R agonist CGS21680 increased the frequency of calcium sparks from 0.12+/-0.03 to 0.31+/-0.08 sparks.mum min(-1) (p<0.05) and calcium waves from 0.65+/-0.31 to 5.11+/-1.84 waves.min(-1) (p<0.03) [20].
  • The CGS21680-induced vasodilation was, on average, 34% less in endothelium-denuded arteries [21].

Anatomical context of CGS21680


Associations of CGS21680 with other chemical compounds

  • In the presence of LPS (EC(50) < 10 ng/ml), but not of IFN-gamma, both NECA and CGS21680 synergistically up-regulate VEGF expression by as much as 10-fold [24].
  • Following prolonged PMA treatment to down-regulate susceptible PKC isoforms, CGS21680 but not PMA inhibited the cobalt chloride induction of VEGF mRNA [18].
  • The adenosine A2a-receptor selective antagonist (E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine (KF17837) inhibited both CGS21680-induced COX-2 expression and PGE2 release [25].
  • Here we used electroencephalogram and electromyogram recordings coupled with in vivo microdialysis to investigate the effects of an A(2A)R agonist, CGS21680, on sleep and on the release of histamine and GABA in the brain [26].
  • Prolonged treatment of PC12 cells with an A2A-selective agonist (CGS21680) leads to increased PDE4 activity in a dose-dependent manner, which can be blocked by an A2A-selective antagonist [8-(3-chlorostyryl)caffeine] [27].

Gene context of CGS21680

  • A2B receptors mediate VEGF and IL-8 secretion because neither CGS21680 (selective A2A agonist) nor IB-MECA (selective A3 agonist) produced this effect, and it was inhibited by the selective A2B antagonist IPDX but not by the selective A2A antagonist SCH58261 or the selective A3 antagonist MRS1191 [28].
  • Stimulation of the A2A-R using CGS21680, forskolin, and a constitutively active cAMP-response element-binding protein (CREB) mutant elevated the reduced promoter activity of the A2A-R gene by mutant Htt [29].
  • Co-administration of CGS21680 and quinpirole (D2 receptor agonist) attenuated the expression of zif/268 mRNA in dorsal striatum but not in motor cortex, indicating that the cortical response is dopamine-D2-receptor-independent [30].
  • NECA and CGS21680 increased cAMP production within 10 minutes, and cAMP stimulation increased VEGF mRNA 4.8 +/- 2.6 times (P = 0.034) [31].
  • A single injection of CGS21680 (A2A receptor agonist), induced strong expression of zif/268 mRNA, detected by in situ hybridization, not only in striatum but also in the motor cortex of the "weaver" mutant [30].

Analytical, diagnostic and therapeutic context of CGS21680

  • CGS21680 was continuously administered to rats through a chronically implanted cannula for 6 h during their active phase [32].
  • Microinjection of the A(2A) receptor agonist CGS21680 (0.005-0.5 microg) into the striatum of non-lesioned animals increased GABA concentrations in the globus pallidus, which was abolished by the voltage-dependent Na(+) channel blocker tetrodotoxin (1 micromol/l) delivered locally to the globus pallidus via the dialysis membrane [33].
  • Furthermore, the number of positive CD18 cells (mm(2) myocardium), which was significantly correlated with TUNEL positive cells in peri-necrotic zone, was significantly reduced from 403+/-42 in Control group to 142+/-18* in Ado group and 153+/-20%* in CGS21680 group, respectively [34].
  • Gel mobility shift assays revealed that six CRE-specific DNA-protein complexes were formed, and the amounts of three of them were significantly increased by treatment with CGS21680 [35].
  • 5'-N-ethylcarboxamido-adenosine (NECA; 0.5, 1 mg/kg) and 4-[2-[[6-Amino-9-(N-ethyl-beta-D-ribofuranuronamidosyl)-9H-purin-2 -yl ]amino] ethyl]benzenepropanoic acid (CGS21680; 0.001, 0.01, 0.025, 0. 05 mg/kg), given 1 h before the start of the test, increased morphine self-administration [36].


  1. Direct preconditioning of cultured chick ventricular myocytes. Novel functions of cardiac adenosine A2a and A3 receptors. Strickler, J., Jacobson, K.A., Liang, B.T. J. Clin. Invest. (1996) [Pubmed]
  2. Role of phosphatidylinositol 3-kinase in the development of hepatocyte preconditioning. Carini, R., Grazia De Cesaris, M., Splendore, R., Baldanzi, G., Nitti, M.P., Alchera, E., Filigheddu, N., Domenicotti, C., Pronzato, M.A., Graziani, A., Albano, E. Gastroenterology (2004) [Pubmed]
  3. Promotion of sleep mediated by the A2a-adenosine receptor and possible involvement of this receptor in the sleep induced by prostaglandin D2 in rats. Satoh, S., Matsumura, H., Suzuki, F., Hayaishi, O. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  4. A2A adenosine receptors from rat striatum and rat pheochromocytoma PC12 cells: characterization with radioligand binding and by activation of adenylate cyclase. Hide, I., Padgett, W.L., Jacobson, K.A., Daly, J.W. Mol. Pharmacol. (1992) [Pubmed]
  5. Mu-opioid agonist enhancement of prostaglandin-induced hyperalgesia in the rat: a G-protein beta gamma subunit-mediated effect? Khasar, S.G., Wang, J.F., Taiwo, Y.O., Heller, P.H., Green, P.G., Levine, J.D. Neuroscience (1995) [Pubmed]
  6. CGS21680 attenuates symptoms of Huntington's disease in a transgenic mouse model. Chou, S.Y., Lee, Y.C., Chen, H.M., Chiang, M.C., Lai, H.L., Chang, H.H., Wu, Y.C., Sun, C.N., Chien, C.L., Lin, Y.S., Wang, S.C., Tung, Y.Y., Chang, C., Chern, Y. J. Neurochem. (2005) [Pubmed]
  7. Strong rebound of wakefulness follows prostaglandin D2- or adenosine A2a receptor agonist-induced sleep. Gerashchenko, D., Okano, Y., Urade, Y., Inoué, S., Hayaishi, O. Journal of sleep research. (2000) [Pubmed]
  8. Expression pattern of FOS in orexin neurons during sleep induced by an adenosine A2A receptor agonist. Satoh, S., Matsumura, H., Kanbayashi, T., Yoshida, Y., Urakami, T., Nakajima, T., Kimura, N., Nishino, S., Yoneda, H. Behav. Brain Res. (2006) [Pubmed]
  9. Adenosine A2b receptors evoke interleukin-8 secretion in human mast cells. An enprofylline-sensitive mechanism with implications for asthma. Feoktistov, I., Biaggioni, I. J. Clin. Invest. (1995) [Pubmed]
  10. Activation of Th1 and Tc1 cell adenosine A2A receptors directly inhibits IL-2 secretion in vitro and IL-2-driven expansion in vivo. Erdmann, A.A., Gao, Z.G., Jung, U., Foley, J., Borenstein, T., Jacobson, K.A., Fowler, D.H. Blood (2005) [Pubmed]
  11. Adenosine receptor occupancy suppresses chemoattractant-induced phospholipase D activity by diminishing membrane recruitment of small GTPases. Thibault, N., Harbour, D., Borgeat, P., Naccache, P.H., Bourgoin, S.G. Blood (2000) [Pubmed]
  12. Expression and pharmacological characterization of a stimulatory subtype of adenosine receptor in fetal chick ventricular myocytes. Xu, D., Kong, H.Y., Liang, B.T. Circ. Res. (1992) [Pubmed]
  13. A3 adenosine receptor activation triggers phosphorylation of protein kinase B and protects rat basophilic leukemia 2H3 mast cells from apoptosis. Gao, Z., Li, B.S., Day, Y.J., Linden, J. Mol. Pharmacol. (2001) [Pubmed]
  14. Characterization of adenosine receptors evoking excitation of mesenteric afferents in the rat. Kirkup, A.J., Eastwood, C., Grundy, D., Chessell, I.P., Humphrey, P.P. Br. J. Pharmacol. (1998) [Pubmed]
  15. Actions of adenosine A2A receptor antagonist KW-6002 on drug-induced catalepsy and hypokinesia caused by reserpine or MPTP. Shiozaki, S., Ichikawa, S., Nakamura, J., Kitamura, S., Yamada, K., Kuwana, Y. Psychopharmacology (Berl.) (1999) [Pubmed]
  16. Differential effects of adenosine receptor subtypes on release and reuptake of hippocampal serotonin. Okada, M., Kawata, Y., Murakami, T., Wada, K., Mizuno, K., Kondo, T., Kaneko, S. Eur. J. Neurosci. (1999) [Pubmed]
  17. Signal pathway involved in the development of hypoxic preconditioning in rat hepatocytes. Carini, R., De Cesaris, M.G., Splendore, R., Vay, D., Domenicotti, C., Nitti, M.P., Paola, D., Pronzato, M.A., Albano, E. Hepatology (2001) [Pubmed]
  18. Distinct protein kinase C isoforms mediate regulation of vascular endothelial growth factor expression by A2A adenosine receptor activation and phorbol esters in pheochromocytoma PC12 cells. Gardner, A.M., Olah, M.E. J. Biol. Chem. (2003) [Pubmed]
  19. Characterization of two affinity states of adenosine A2a receptors with a new radioligand, 2-[2-(4-amino-3-[125I]iodophenyl)ethylamino]adenosine. Luthin, D.R., Olsson, R.A., Thompson, R.D., Sawmiller, D.R., Linden, J. Mol. Pharmacol. (1995) [Pubmed]
  20. Adenosine A(2A) receptors are expressed in human atrial myocytes and modulate spontaneous sarcoplasmic reticulum calcium release. Hove-Madsen, L., Prat-Vidal, C., Llach, A., Ciruela, F., Casad??, V., Lluis, C., Bayes-Genis, A., Cinca, J., Franco, R. Cardiovasc. Res. (2006) [Pubmed]
  21. Role of K+ channels in A2A adenosine receptor-mediated dilation of the pressurized renal arcuate artery. Prior, H.M., Yates, M.S., Beech, D.J. Br. J. Pharmacol. (1999) [Pubmed]
  22. Gs protein-coupled adenosine receptor signaling and lytic function of activated NK cells. Raskovalova, T., Huang, X., Sitkovsky, M., Zacharia, L.C., Jackson, E.K., Gorelik, E. J. Immunol. (2005) [Pubmed]
  23. Pharmacological analysis of calcium responses mediated by the human A3 adenosine receptor in monocyte-derived dendritic cells and recombinant cells. Fossetta, J., Jackson, J., Deno, G., Fan, X., Du, X.K., Bober, L., Soudé-Bermejo, A., de Bouteiller, O., Caux, C., Lunn, C., Lundell, D., Palmer, R.K. Mol. Pharmacol. (2003) [Pubmed]
  24. Synergistic up-regulation of vascular endothelial growth factor expression in murine macrophages by adenosine A(2A) receptor agonists and endotoxin. Leibovich, S.J., Chen, J.F., Pinhal-Enfield, G., Belem, P.C., Elson, G., Rosania, A., Ramanathan, M., Montesinos, C., Jacobson, M., Schwarzschild, M.A., Fink, J.S., Cronstein, B. Am. J. Pathol. (2002) [Pubmed]
  25. Cyclooxygenase-2 expression in rat microglia is induced by adenosine A2a-receptors. Fiebich, B.L., Biber, K., Lieb, K., van Calker, D., Berger, M., Bauer, J., Gebicke-Haerter, P.J. Glia (1996) [Pubmed]
  26. An adenosine A receptor agonist induces sleep by increasing GABA release in the tuberomammillary nucleus to inhibit histaminergic systems in rats. Hong, Z.Y., Huang, Z.L., Qu, W.M., Eguchi, N., Urade, Y., Hayaishi, O. J. Neurochem. (2005) [Pubmed]
  27. Activation of phosphodiesterase IV during desensitization of the A2A adenosine receptor-mediated cyclic AMP response in rat pheochromocytoma (PC12) cells. Chang, Y.H., Conti, M., Lee, Y.C., Lai, H.L., Ching, Y.H., Chern, Y. J. Neurochem. (1997) [Pubmed]
  28. Mast cell-mediated stimulation of angiogenesis: cooperative interaction between A2B and A3 adenosine receptors. Feoktistov, I., Ryzhov, S., Goldstein, A.E., Biaggioni, I. Circ. Res. (2003) [Pubmed]
  29. cAMP-response element-binding protein contributes to suppression of the A2A adenosine receptor promoter by mutant Huntingtin with expanded polyglutamine residues. Chiang, M.C., Lee, Y.C., Huang, C.L., Chern, Y. J. Biol. Chem. (2005) [Pubmed]
  30. Stimulation of adenosine A2A receptors elicits zif/268 and NMDA epsilon2 subunit mRNA expression in cortex and striatum of the "weaver" mutant mouse, a genetic model of nigrostriatal dopamine deficiency. Ekonomou, A., Poulou, P.D., Matsokis, N., Angelatou, F. Neuroscience (2004) [Pubmed]
  31. Adenosine mediates hypoxic induction of vascular endothelial growth factor in retinal pericytes and endothelial cells. Takagi, H., King, G.L., Robinson, G.S., Ferrara, N., Aiello, L.P. Invest. Ophthalmol. Vis. Sci. (1996) [Pubmed]
  32. Region-dependent difference in the sleep-promoting potency of an adenosine A2A receptor agonist. Satoh, S., Matsumura, H., Koike, N., Tokunaga, Y., Maeda, T., Hayaishi, O. Eur. J. Neurosci. (1999) [Pubmed]
  33. Systemic administration of adenosine A(2A) receptor antagonist reverses increased GABA release in the globus pallidus of unilateral 6-hydroxydopamine-lesioned rats: a microdialysis study. Ochi, M., Koga, K., Kurokawa, M., Kase, H., Nakamura, J., Kuwana, Y. Neuroscience (2000) [Pubmed]
  34. Adenosine attenuates reperfusion-induced apoptotic cell death by modulating expression of Bcl-2 and Bax proteins. Zhao, Z.Q., Budde, J.M., Morris, C., Wang, N.P., Velez, D.A., Muraki, S., Guyton, R.A., Vinten-Johansen, J. J. Mol. Cell. Cardiol. (2001) [Pubmed]
  35. Stimulation of the A2A adenosine receptor increases expression of the tyrosine hydroxylase gene. Chae, H.D., Kim, K.T. Brain Res. Mol. Brain Res. (1997) [Pubmed]
  36. Adenosine A(2) receptors inhibit morphine self-administration in rats. Sahraei, H., Motamedi, F., Khoshbaten, A., Zarrindast, M.R. Eur. J. Pharmacol. (1999) [Pubmed]
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