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Chemical Compound Review

PubChem2676     2-(9-methoxy-7,10- dioxabicyclo[4.4.0]deca...

Synonyms: CHEMBL10332, SureCN2494824, KBioSS_002301, CHEBI:73287, CHEBI:106680, ...
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Disease relevance of nchembio705-4

  • The hypotension induced by rilmenidine in the rostral ventrolateral medulla was completely reversed both by 2-methoxyidazoxan and by idazoxan, as was the sympathetic inhibition [1].
  • 4. Pretreatment with the selective alpha 2-adrenoceptor antagonist, RX 821002 (0.1-3.0 mg kg-1, i.p.) 45 min before EEDQ prevented the loss of alpha 2-adrenoceptors as well as the blockade of medetomide-induced sedation and hypothermia by EEDQ [2].
  • 2. The more selective and specific alpha 2-adrenoceptor antagonists, RX811059 (0.3, 1, 3 mg kg-1, i.p.) and RX821002 (0.3, 1, 3 mg kg-1, i.p.), did not produce hyperphagia in rats, however, the highest dose produced a significant increase in water intake [3].
  • 3. The 7-day treatment with RX 821002 or idazoxan failed to influence food intake, total body weight or perirenal adipose tissue weight [4].
  • However, PHFD was attenuated significantly more in RX821002-treated vs. sham rats (-3+/-3 bursts/min vs. -12+/-4 bursts/min @ 5 min post hypoxia for RX821002 and sham-treated, respectively; p<0.05) [5].

Psychiatry related information on nchembio705-4

  • RESULTS: It was found that: (1) both RX 821002 and yohimbine statistically significantly reduced choice accuracy dose- and delay-dependently and in a similar magnitude to that of scopolamine while modifying the motor aspects of task performance delay-independently and (2) RX 821002 produced mainly rate-decreasing effects [6].

High impact information on nchembio705-4

  • The decrease of [3H] RX821002 binding sites after a 48-h period of treatment reached 70-75% with 170 nM insulin, and a half-maximal effect was observed at 2.6 nM [7].
  • The alpha 2-adrenoceptor antagonist [3H] RX821002 bound to a single site in hypothalamus, preoptic area, and cortex membranes, with high affinity and low nonspecific binding, as determined by Scatchard and kinetic binding analyses [8].
  • Binding of [3H]idazoxan and of its methoxy derivative [3H] RX821002 in human fat cells: [3H]idazoxan but not [3H] RX821002 labels additional non-alpha 2-adrenergic binding sites [9].
  • Effects of a single intravenous dose of rilmenidine (445 mug/kg) on the renal sympathetic nerve activity (RSNA) baroreflex were examined before and after microinjection into the RVLM of the mixed imidazoline/alpha2-adrenoceptor antagonist idazoxan and the alpha2-adrenoceptor antagonist 2-methoxyidazoxan (2-MI) [10].
  • This effect is abolished by complete section of the spinal cord but not by the selective alpha(2)-adrenoceptor antagonist RX 821002 (Clarke RW, Parry-Baggott C, Houghton AK, Ogilvie J. The involvement of bulbo-spinal pathways in fentanyl-induced inhibition of spinal withdrawal reflexes in the decerebrated rabbit. Pain 1998;78:197-207) [11].

Chemical compound and disease context of nchembio705-4

  • Two groups of rats were then administered either: (1) saline (sham) or (2) the alpha2-receptor antagonist, RX821002 HCl (2-[2-(2-Methoxy-1,4-benzodioxanyl)] imidazoline hydrochloride; 0.25 mg/kg, i.v.). Isocapnic hypoxia was repeated 10 min later [5].

Biological context of nchembio705-4

  • Neither the I(2)-ligands nor the MAO inhibitors prevented the further enhancement of reflexes or blood pressure by subsequent administration of the selective alpha(2)-adrenoceptor antagonist RX 821002 [12].
  • 5. The lack of effect RX811059 and RX821002 on food intake contrasts with the large dose-related increases induced by idazoxan and suggests that the hyperphagic effects of idazoxan are not due to alpha 2-adrenoceptor blockade but may instead reflect its affinity for a non-adrenoceptor site, a property not shared by the other alpha 2-antagonists [3].
  • Reflexes evoked in medial gastrocnemius motoneurones by electrical stimulation of the sural nerve were unaffected by intrathecal ( administration of RX 821002 (111 and 664 nmol cumulative, n = 7), although the highest dose of this drug did produce a significant increase in heart rate of 28 +/- 7 beats min(-1) [13].
  • 5. RX821002 is a more potent alpha 2-adrenoceptor antagonist than yohimbine on adrenaline-induced platelet aggregation [14].
  • Moreover, chronic administration of idazoxan and RX821002 to adult rabbits (4 mg/kg, subcutaneously for 7 days), resulted in an up-regulation of alpha 2-adrenoceptors in fat cells while the number of NAIBS was unaffected by the treatment [15].

Anatomical context of nchembio705-4

  • Pre-treatment of rat whole brain membranes by BU99006, or by the alpha(2)-adrenoceptor antagonists RX821002 or rauwolscine had no effect on the specific binding of [(3)H]RX821002 [16].
  • The authors compared [3H]2-methoxy-idazoxan (RX 821002) and [3H]rauwolscine binding in rat cerebral cortex, spleen and kidney; guinea pig kidney; porcine kidney; human kidney and platelets and HEL and NG 108-15 cells [17].
  • 4. RX 821002 and idazoxan increased the number of [3H]-RX 821002 binding sites in adipose tissue with no change in colocytes or platelets [4].
  • Does [3H]2-methoxy-idazoxan (RX 821002) detect more alpha-2-adrenoceptor agonist high-affinity sites than [3H]rauwolscine? A comparison of nine tissues and cell lines [17].
  • Competition studies with yohimbine and RX 821002 showed decreases in [(11)C]mirtazapine pB throughout the forebrain; use of the multireceptor version of the Michaelis-Menten equation indicated that 42% of [(11)C]mirtazapine binding in cortical regions is displaceable by yohimbine [18].

Associations of nchembio705-4 with other chemical compounds

  • Perfusion with RX821002 produced a significant increase in K+-induced release of noradrenaline that returned to normal basal values before the end of the stimulation period [19].
  • 5. S-22068 did not interact with the sulphonylurea binding site nor with the non-I1 and non-I2 imidazoline site evidenced in the beta cells that is recognized by the imidazoline compounds efaroxan, phentolamine and RX821002 [20].
  • In the cerebral cortex of WKY and SHR rats, the rank order of potency of imidazoli(di)ne drugs (cirazoline greater than idazoxan greater than naphazoline greater than clonidine much greater than RX821002) competing with [3H]idazoxan showed the specificity for an imidazoline receptor which also appeared heterogeneous in nature [21].
  • This effect was blocked by alpha2 adrenergic antagonists, RX 821002 or yohimbine, as well as a alpha2A selective antagonist, BRL 44408, but not by alpha2B/alpha2C selective antagonists ARC 239, imiloxan and rauwolscine [22].
  • Both the I(2) binding site selective ligand BU224 (10 mg kg(-1) i.p.) and the alpha(2)-adrenoceptor antagonist RX821002 (2.5 mg kg(-1) i.p.) significantly elevated extracellular levels of NA in the PVN region and plasma corticosterone (CORT) in a rapid and transient manner in both control and AA rats [23].

Gene context of nchembio705-4

  • In contrast, RX821002 had no effect on forskolin-stimulated cAMP accumulation in striatal slices from Adra2c-/- mice or in striatal slices from Adra2c+/+ mice treated with reserpine and alpha-methyl-rho-tyrosine to deplete monoamine neurotransmitters [24].
  • In the hot-plate test in mice, the antinociceptive action of the alpha 2-adrenoceptor agonist, UK 14,304, was abolished by the alpha 2-adrenoceptor antagonist, idazoxan, the potent alpha 2A-adrenoceptor antagonist, RX 821002 and the preferential alpha 2A-adrenoceptor antagonist, BRL 44408 [25].
  • Yohimbine and 2-(2,3-dihydro-2-methoxy-1,4-benzodioxin-2-yl)4,5-dihydro-1H-imidazole (RX821002), alpha(2)-adrenoceptor antagonists, significantly blocked agonist-induced interleukin-12 production and p38 MAPK activation, indicating that the effects of the agonists were mediated through alpha(2)-adrenoceptor [26].
  • Both atipamezo 1 e (1 mg/kg) and RX 821002 (0.06-0.2 mg/kg) significantly attenuated ethanol-induced hypothermia, ataxia and reduction in head-dipping, but were without effect on ethanol-induced locomotor stimulation [27].
  • 2. In dogs with intact autonomic reflexes, 2-methoxyidazoxan (15 micrograms kg-1 plus 0.6 micrograms kg-1 min-1) produced effects consistent with a generalized increase in sympathetic drive, including increases in mean arterial pressure and plasma renin activity, and a reduction in sodium excretion [28].

Analytical, diagnostic and therapeutic context of nchembio705-4

  • Nefopam was shown to possess RX821002-reversible antinociceptive activity in both the tail immersion test and the abdominal constriction assay [29].
  • Following a period of immobilization during which radiotelemetry collars were fitted, the animals were revived using idazoxan (RX 781094) or its methoxy analogue RX 821002 [30].


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  2. Covariation of alpha 2-adrenoceptor density and function following irreversible antagonism with EEDQ. Durcan, M.J., Morgan, P.F., Van Etten, M.L., Linnoila, M. Br. J. Pharmacol. (1994) [Pubmed]
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  4. Effect of a 7-day treatment with idazoxan and its 2-methoxy derivative RX 821002 [correction of RX 821001] on alpha 2-adrenoceptors and non-adrenoceptor idazoxan binding sites in rabbits. Portillo, M., Reverte, M., Langin, D., Senard, J.M., Tran, M.A., Berlan, M., Montastruc, J.L. Br. J. Pharmacol. (1991) [Pubmed]
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  7. Regulation of the alpha 2A-adrenergic receptor in the HT29 cell line. Effects of insulin and growth factors. Devedjian, J.C., Fargues, M., Denis-Pouxviel, C., Daviaud, D., Prats, H., Paris, H. J. Biol. Chem. (1991) [Pubmed]
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  9. Binding of [3H]idazoxan and of its methoxy derivative [3H] RX821002 in human fat cells: [3H]idazoxan but not [3H] RX821002 labels additional non-alpha 2-adrenergic binding sites. Langin, D., Paris, H., Lafontan, M. Mol. Pharmacol. (1990) [Pubmed]
  10. Contribution of imidazoline receptors and alpha2-adrenoceptors in the rostral ventrolateral medulla to sympathetic baroreflex inhibition by systemic rilmenidine. Chan, C.K., Burke, S.L., Head, G.A. J. Hypertens. (2007) [Pubmed]
  11. The role of 5-HT(1A)-receptors in fentanyl-induced bulbospinal inhibition of a spinal withdrawal reflex in the rabbit. Clarke, R.W., Ward, R.E. Pain (2000) [Pubmed]
  12. Imidazoline I(2)-receptors and spinal reflexes in the decerebrated rabbit. Clarke, R.W., Harris, J., Ogilvie, J. Neuropharmacology (2000) [Pubmed]
  13. Effect of RX 821002 at 5-HT1A-receptors in rabbit spinal cord in vivo. Ogilvie, J., Clarke, R.W. Br. J. Pharmacol. (1998) [Pubmed]
  14. Identification of human platelet alpha 2-adrenoceptors with a new antagonist [3H]-RX821002, a 2-methoxy derivative of idazoxan. Galitzky, J., Senard, J.M., Lafontan, M., Stillings, M., Montastruc, J.L., Berlan, M. Br. J. Pharmacol. (1990) [Pubmed]
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  16. 5-Isothiocyanato-2-benzofuranyl-2-imidazoline (BU99006) an irreversible imidazoline(2) binding site ligand: in vitro and in vivo characterisation in rat brain. Tyacke, R.J., Robinson, E.S., Nutt, D.J., Hudson, A.L. Neuropharmacology (2002) [Pubmed]
  17. Does [3H]2-methoxy-idazoxan (RX 821002) detect more alpha-2-adrenoceptor agonist high-affinity sites than [3H]rauwolscine? A comparison of nine tissues and cell lines. Erdbrügger, W., Raulf, M., Otto, T., Michel, M.C. J. Pharmacol. Exp. Ther. (1995) [Pubmed]
  18. Inhibition of [(11)C]mirtazapine binding by alpha(2)-adrenoceptor antagonists studied by positron emission tomography in living porcine brain. Smith, D.F., Dyve, S., Minuzzi, L., Jakobsen, S., Munk, O.L., Marthi, K., Cumming, P. Synapse (2006) [Pubmed]
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  20. In vitro mechanism of action on insulin release of S-22068, a new putative antidiabetic compound. Le Brigand, L., Virsolvy, A., Manechez, D., Godfroid, J.J., Guardiola-Lemaître, B., Gribble, F.M., Ashcroft, F.M., Bataille, D. Br. J. Pharmacol. (1999) [Pubmed]
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  24. alpha2C adrenoceptors inhibit adenylyl cyclase in mouse striatum: potential activation by dopamine. Zhang, W., Klimek, V., Farley, J.T., Zhu, M.Y., Ordway, G.A. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  25. Evidence that an alpha 2A-adrenoceptor subtype mediates antinociception in mice. Millan, M.J. Eur. J. Pharmacol. (1992) [Pubmed]
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  27. Evidence for central alpha-2 adrenoceptors, not imidazoline binding sites, mediating the ethanol-attenuating properties of alpha-2 adrenoceptor antagonists. Durcan, M.J., Lister, R.G., Linnoila, M. J. Pharmacol. Exp. Ther. (1991) [Pubmed]
  28. Renal effects of infusion of rilmenidine and guanabenz in conscious dogs: contribution of peripheral and central nervous system alpha 2-adrenoceptors. Evans, R.G., Anderson, W.P. Br. J. Pharmacol. (1995) [Pubmed]
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  30. Evaluation of xylazine hydrochloride as the sole immobilizing agent in moose and caribou--and its subsequent reversal with idazoxan. Doherty, T.J., Tweedie, D.P. J. Wildl. Dis. (1989) [Pubmed]
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