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Chemical Compound Review

Tocris-1036     4-[2-[[2-amino-8-(2-furyl)- 1,3,5,7,9...

Synonyms: PubChem16764, CHEMBL113142, SureCN194966, QC-8166, BCPP000003, ...
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Disease relevance of Tocris-1036

  • Analogously, the application of CHPG potentiated NMDA-induced toxicity (measured by LDH release) in cultured striatal neurons, an effect that was abolished by both MPEP and ZM 241385 [1].
  • Gestational diabetes and NBMPR effects involved eNOS, PKC and p42/44(mapk) activation, and were blocked by the A(2a) purinoceptor antagonist ZM-241385 [2].
  • Isocapnic hypoxia with infusion of DPCPX or the vehicle for DPCPX or ZM-241385 produced a transient fall in HR, a rise in MAP, and a decrease in plasma volume [3].
  • RESULTS: ZM 241385 increased TES-induced contractions in the absence or in the presence of colitis, the drug being more effective in colonic preparations from inflamed animals [4].
  • Neither Theo nor ZM-241385 affected vascular reactivity to mild hypercapnia induced by 5% CO(2) inhalation [5].

High impact information on Tocris-1036

  • In contrast, MRE0094 stimulated a dose-dependent increase in cAMP levels in TNF-alpha-treated cells that was almost completely blocked by the A(2A) receptor antagonist ZM-241385 (4-[2-[7-amino-2-(2-furyl)[1,2,4]triazolo-[2,3-a][1,3,5]triazin-5-ylamino]ethyl]phenol) [6].
  • CGS21680 potentiation of lipopolysaccharide-induced NO release was suppressed by the A2A receptor antagonist ZM-241385 and did not occur on mixed glial cultures from A2A receptor-deficient mice [7].
  • Endogenous tone at A(2A)Rs seemed to be required to enable mGlu5R-mediated effects, as the ability of CHPG to potentiate NMDA effects was antagonized by the selective A(2A)R antagonist ZM 241385 in rat hippocampal slices and cultured hippocampal neurons, and abolished in the hippocampus of A(2A)R knockout mice [8].
  • The [1,2,4]triazolo[1,5-a]triazine derivative 3, more commonly known in the field of adenosine research as ZM-241385, has previously been demonstrated to be a potent and selective adenosine A2a receptor antagonist, although with limited oral bioavailability [9].
  • The A2a/A2b receptor antagonist ZM-241385 blocks the cardioprotective effect of adenosine agonist pretreatment in in vivo rat myocardium [10].

Chemical compound and disease context of Tocris-1036

  • DPCPX blunted the bradycardia associated with CCPA and NECA, whereas ZM-241385 attenuated their hypotensive effects [10].
  • ZM 241385 reversed the beneficial effect of ketamine on survival from bacterial sepsis [11].
  • In contrast, an equimolar dose of the selective adenosine A(2A) antagonist 4-(2-[7-amino-2-(2-furyl)1,2,4-triazolo[2,3-a]-[1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385) (5.15 micromol/kg) produced a significant reduction of catalepsy intensity and increased catalepsy latency [12].
  • METHODS: Theophylline (36 mg/kg), ZM 241385 (1 mg/kg), or an equivalent volume of saline was administered to rats intraperitoneally 30 minutes before ischemia was induced [13].
  • Chronically catheterized lambs of 7-16 days of age breathed via face mask a gas mixture with a fraction of inspired O2 of 0.21 (normoxia) or 0.07 (hypoxia), while being infused intravascularly with 9-cyclopentyl-1,3-dipropylxanthine (DPCPX; ADO A1-receptor antagonist, n=8), ZM-241385 (ADO A2A-receptor antagonist, n=7), or vehicle [14].

Biological context of Tocris-1036

  • Moreover, NECA-induced vasodilation was suppressed by alloxazine (1 micromol/l) but not by ZM-241385 (1 micromol/l, A(2A) antagonist), which suggests mediation by A(2B)- receptor activation [15].
  • Inhibition of A(2A)AR with ZM-241385, a known A(2A)AR antagonist, impeded wound healing [16].
  • Intra-arterial infusion of ZM-241385, an antagonist highly selective for ADO A(2A) receptors, to eight fetuses during normoxia significantly increased mean arterial pressure (MAP) from 42.5 +/- 2.0 to 46.1 +/- 2.0 mmHg without altering heart rate (HR) [3].
  • 3. The A(2A) receptor antagonist, ZM 241385 (10 nM) as well as adenosine deaminase (ADA, 2 U ml(-1)), prevented the enhancement of field EPSP slope caused by CGRP (30 nM) in the presence of DPCPX (10 nM), suggesting that this effect of CGRP requires the concomitant activation of A(2A) adenosine receptors by endogenous adenosine [17].
  • Membrane potential changes were persistent (>10 min) and could be blocked by the selective A2A receptor antagonist ZM-241385, or GDP-beta-S, the latter suggesting postsynaptic sites of action [18].

Anatomical context of Tocris-1036


Associations of Tocris-1036 with other chemical compounds

  • 3. ZM 241385 had low potency at A2b receptors and antagonized the relaxant effects of adenosine in the guinea-pig aorta with a pA2 of 7.06, (c.l., 6.92-7.19) [19].
  • In guinea-pig isolated Langendorff hearts, ZM 241385 antagonized vasodilatation of the coronary bed produced by 2-chloroadenosine (2-CADO) and 2-[p-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680) with pA2 values of 8.57 (c.l., 8.45-8.68) and 9.02 (c.l., 8.79-9.24) respectively [19].
  • Upon exposure of colonic tissues from normal or inflamed rats to dipyridamole plus adenosine deaminase, to abate endogenous adenosine levels, CGS 21680 evoked concentration-dependent reductions of contractile responses to TES, which were more intense in preparations from inflamed rats, and were antagonized by ZM 241385 [4].
  • 1. This paper describes the in vitro pharmacology of ZM 241385 (4-(2-[7-amino-2-(2-furyl) [1,2,4]-triazolo[2,3-a][1,3,5]triazin- 5-yl amino]ethyl) phenol), a novel non-xanthine adenosine receptor antagonist with selectivity for the A2a receptor subtype [19].
  • The effects of ZM 241385 (A2a receptor antagonist) and CGS 21680 (A2a receptor agonist) were assayed on cholinergic contractions of colonic longitudinal muscle preparations evoked by transmural electrical stimulation (TES) or carbachol [4].

Gene context of Tocris-1036

  • This effect was prevented by the A2AR antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM-241385) [23].
  • The action of BDNF was prevented by the adenosine A(2A) receptor antagonist, ZM 241385 (50 nM) as well as by the TrkB receptor phosphorylation inhibitor, K252a (200 nM) [24].
  • The selective adenosine A2A receptor antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385, 100 nm) did not modify the magnitude of fepsp recovery compared to control slices [25].
  • Chlorofuryl-triazolo-quinazolinamine (CGS-15943; 1 micromol/L), an adenosine A1 and A2 receptor antagonist, and aminofuryltriazolotriazinyl-aminoethylphenol (ZM-241385; 1 micromol/L), a selective adenosine A2a receptor antagonist, inhibited the effect of CGS-21680 [26].
  • Furthermore, the antinociceptive effects of 5'd-5IT were completely blocked by an ADO A1 receptor selective antagonist, DPCPX, while an ADO A2A receptor selective antagonist, ZM 241385, showed markedly less antagonist activity [27].

Analytical, diagnostic and therapeutic context of Tocris-1036

  • Intrastriatal perfusion of ZM 241385 (50-100 microM) had no effect on basal extracellular DA level, but enhanced dose-dependently the l-DOPA-induced DA release in intact and malonate-lesioned animals [28].
  • Quantitative Western blot analysis demonstrated that the density of A2A receptors increased in ZM 241385-treated artery [22].
  • Recipients were given either saline (control group) or CGS 21680 (2-p-(2-Carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride, a selective A(2A)R agonist), or CGS 21680+ ZM 241385 (a selective A(2A)R antagonist) immediately after reperfusion for 3 h [29].


  1. Permissive role of adenosine A2A receptors on metabotropic glutamate receptor 5 (mGluR5)-mediated effects in the striatum. Domenici, M.R., Pepponi, R., Martire, A., Tebano, M.T., Potenza, R.L., Popoli, P. J. Neurochem. (2004) [Pubmed]
  2. Role of adenosine transport in gestational diabetes-induced L-arginine transport and nitric oxide synthesis in human umbilical vein endothelium. Vásquez, G., Sanhueza, F., Vásquez, R., González, M., San Martín, R., Casanello, P., Sobrevia, L. J. Physiol. (Lond.) (2004) [Pubmed]
  3. Adenosine A(2A) receptors mediate cardiovascular responses to hypoxia in fetal sheep. Koos, B.J., Maeda, T. Am. J. Physiol. Heart Circ. Physiol. (2001) [Pubmed]
  4. A2a receptors mediate inhibitory effects of adenosine on colonic motility in the presence of experimental colitis. Antonioli, L., Fornai, M., Colucci, R., Ghisu, N., Blandizzi, C., Del Tacca, M. Inflamm. Bowel Dis. (2006) [Pubmed]
  5. Adenosine receptors mediate glutamate-evoked arteriolar dilation in the rat cerebral cortex. Iliff, J.J., D'Ambrosio, R., Ngai, A.C., Winn, H.R. Am. J. Physiol. Heart Circ. Physiol. (2003) [Pubmed]
  6. Th1 cytokines regulate adenosine receptors and their downstream signaling elements in human microvascular endothelial cells. Nguyen, D.K., Montesinos, M.C., Williams, A.J., Kelly, M., Cronstein, B.N. J. Immunol. (2003) [Pubmed]
  7. Adenosine A2A receptor stimulation potentiates nitric oxide release by activated microglia. Saura, J., Angulo, E., Ejarque, A., Casadó, V., Tusell, J.M., Moratalla, R., Chen, J.F., Schwarzschild, M.A., Lluis, C., Franco, R., Serratosa, J. J. Neurochem. (2005) [Pubmed]
  8. Adenosine A2A receptors and metabotropic glutamate 5 receptors are co-localized and functionally interact in the hippocampus: a possible key mechanism in the modulation of N-methyl-D-aspartate effects. Tebano, M.T., Martire, A., Rebola, N., Pepponi, R., Domenici, M.R., Grò, M.C., Schwarzschild, M.A., Chen, J.F., Cunha, R.A., Popoli, P. J. Neurochem. (2005) [Pubmed]
  9. Piperazine derivatives of [1,2,4]triazolo[1,5-a][1,3,5]triazine as potent and selective adenosine A2a receptor antagonists. Vu, C.B., Peng, B., Kumaravel, G., Smits, G., Jin, X., Phadke, D., Engber, T., Huang, C., Reilly, J., Tam, S., Grant, D., Hetu, G., Chen, L., Zhang, J., Petter, R.C. J. Med. Chem. (2004) [Pubmed]
  10. The A2a/A2b receptor antagonist ZM-241385 blocks the cardioprotective effect of adenosine agonist pretreatment in in vivo rat myocardium. Lasley, R.D., Kristo, G., Keith, B.J., Mentzer, R.M. Am. J. Physiol. Heart Circ. Physiol. (2007) [Pubmed]
  11. Involvement of adenosine in the antiinflammatory action of ketamine. Mazar, J., Rogachev, B., Shaked, G., Ziv, N.Y., Czeiger, D., Chaimovitz, C., Zlotnik, M., Mukmenev, I., Byk, G., Douvdevani, A. Anesthesiology (2005) [Pubmed]
  12. Selective A2A, but not A1 adenosine antagonists enhance the anticataleptic action of trihexyphenidyl in rats. Villanueva-Toledo, J., Moo-Puc, R.E., Góngora-Alfaro, J.L. Neurosci. Lett. (2003) [Pubmed]
  13. Hippocampal injury and neurobehavioral deficits following hyperglycemic cerebral ischemia: effect of theophylline and ZM 241385. Higashi, H., Meno, J.R., Marwaha, A.S., Winn, H.R. J. Neurosurg. (2002) [Pubmed]
  14. Adenosine A2A-receptor blockade abolishes the roll-off respiratory response to hypoxia in awake lambs. Koos, B.J., Kawasaki, Y., Kim, Y.H., Bohorquez, F. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2005) [Pubmed]
  15. Role of adenosine A(2B) receptors in vasodilation of rat pial artery and cerebral blood flow autoregulation. Shin, H.K., Shin, Y.W., Hong, K.W. Am. J. Physiol. Heart Circ. Physiol. (2000) [Pubmed]
  16. Adenosine A2A receptors promote adenosine-stimulated wound healing in bronchial epithelial cells. Allen-Gipson, D.S., Wong, J., Spurzem, J.R., Sisson, J.H., Wyatt, T.A. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  17. Tonic activation of A(2A) adenosine receptors unmasks, and of A(1) receptors prevents, a facilitatory action of calcitonin gene-related peptide in the rat hippocampus. Sebastião, A.M., Macedo, M.P., Ribeiro, J.A. Br. J. Pharmacol. (2000) [Pubmed]
  18. Activation of adenosine A2A receptors alters postsynaptic currents and depolarizes neurons of the supraoptic nucleus. Ponzio, T.A., Wang, Y.F., Hatton, G.I. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
  19. The in vitro pharmacology of ZM 241385, a potent, non-xanthine A2a selective adenosine receptor antagonist. Poucher, S.M., Keddie, J.R., Singh, P., Stoggall, S.M., Caulkett, P.W., Jones, G., Coll, M.G. Br. J. Pharmacol. (1995) [Pubmed]
  20. Accelerated resequestration of cytosolic calcium and suppression of the pro-inflammatory activities of human neutrophils by CGS 21680 in vitro. Anderson, R., Visser, S.S., Ramafi, G., Theron, A.J. Br. J. Pharmacol. (2000) [Pubmed]
  21. Potentiation of cytokine induction of group IIA phospholipase A(2) in rat mesangial cells by ATP and adenosine via the A2A adenosine receptor. Scholz-Pedretti, K., Pfeilschifter, J., Kaszkin, M. Br. J. Pharmacol. (2001) [Pubmed]
  22. Modulation of A2A adenosine receptors and associated Galphas proteins by ZM 241385 treatment of porcine coronary artery. Rekik, M., Mustafa, J.S. J. Cardiovasc. Pharmacol. (2003) [Pubmed]
  23. Contractile effects of adenosine A1 and A2A receptors in isolated murine hearts. Tikh, E.I., Fenton, R.A., Dobson, J.G. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  24. Triggering of BDNF facilitatory action on neuromuscular transmission by adenosine A2A receptors. Pousinha, P.A., Diogenes, M.J., Ribeiro, J.A., Sebastião, A.M. Neurosci. Lett. (2006) [Pubmed]
  25. Brief, repeated, oxygen-glucose deprivation episodes protect neurotransmission from a longer ischemic episode in the in vitro hippocampus: role of adenosine receptors. Pugliese, A.M., Latini, S., Corradetti, R., Pedata, F. Br. J. Pharmacol. (2003) [Pubmed]
  26. Adenosine A2a receptors increase arterial endothelial cell nitric oxide. Li, J., Fenton, R.A., Wheeler, H.B., Powell, C.C., Peyton, B.D., Cutler, B.S., Dobson, J.G. J. Surg. Res. (1998) [Pubmed]
  27. Characterization of the effects of adenosine kinase inhibitors on acute thermal nociception in mice. Kowaluk, E.A., Kohlhaas, K.L., Bannon, A., Gunther, K., Lynch, J.J., Jarvis, M.F. Pharmacol. Biochem. Behav. (1999) [Pubmed]
  28. Striatal adenosine A(2A) receptor blockade increases extracellular dopamine release following l-DOPA administration in intact and dopamine-denervated rats. Gołembiowska, K., Dziubina, A. Neuropharmacology (2004) [Pubmed]
  29. Protective effect of adenosine A(2A) receptor activation in small-for-size liver transplantation. Tang, L.M., Wang, Y.P., Wang, K., Pu, L.Y., Zhang, F., Li, X.C., Kong, L.B., Sun, B.C., Li, G.Q., Wang, X.H. Transpl. Int. (2007) [Pubmed]
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