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Chemical Compound Review

Norcynt     4-chloro-N-(4,5-dihydro-1H- imidazol-2-yl)...

Synonyms: moxonidin, MOXONIDINE, Moxonidina, Normoxocin, Nucynt, ...
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Disease relevance of Physiotens


Psychiatry related information on Physiotens

  • Non-adrenergic exploratory behavior induced by moxonidine at mildly hypotensive doses [6].
  • Intracerebroventricular injection of moxonidine (5 and 20 nmol/1 microl) reduced the ingestion of 1.5% NaCl solution (4.1 +/- 1.1 and 2.9 +/- 2.5 ml/2 h, respectively vs. control = 7.4 +/- 2.1 ml/2 h) and water intake (2.0 +/- 0.6 and 0.3 +/- 0.2 ml/h, respectively vs. control = 13.0 +/- 1.4 ml/h) induced by water deprivation [7].

High impact information on Physiotens


Chemical compound and disease context of Physiotens


Biological context of Physiotens

  • This study examined the effect of chronic moxonidine therapy, at increasing therapeutic doses, on resting peripheral sympathetic activity and vascular resistance and their responses to physiological reflex maneuvers [4].
  • The alpha(2)-adrenoceptor antagonist yohimbine (50 microg per rat) partially yet significantly inhibited moxonidine-stimulated diuresis and natriuresis but not cGMP excretion [16].
  • The sympatholytic antihypertensive agent moxonidine, a centrally acting selective I1-imidazoline receptor modulator (putative agonist), may be beneficial in hypertensive patients with insulin resistance [17].
  • In this cellular model, diacylglycerol (DAG), a second messenger, is generated in response to the putative I1-imidazoline agonist moxonidine [18].
  • We hypothesized that the hypotensive and renal actions of moxonidine may be mediated by atrial natriuretic peptide (ANP), a cardiac peptide involved in pressure and volume homeostasis through its vasodilatory, diuretic, and natriuretic actions [16].

Anatomical context of Physiotens

  • Stimulation of I1-imidazoline receptor with moxonidine increased enzymatic activity of the classical betaII isoform in membranes by about 75% and redistributed the atypical isoform into membranes (40% increase in membrane-bound activity), but the novel isoform of PKC was unaffected [19].
  • However, treatment with aspirin and methylprednisolone, but not moxonidine and captopril, increased capillary to myocyte ratio (P<0.05) up to twice the values of non-treated MI hearts, indicating newly formed capillaries [13].
  • To determine whether reduced IRAS expression attenuated I(1)R cell signaling, PC12 cells transfected with antisense or sense oligo-DNA were treated with moxonidine, an I(1)R agonist, then cell lysates were analyzed by western blot [20].
  • In LLC-PK1 cells moxonidine (10 mumol/liter) had no effect on the basal pH1; however, it reduced the Na+/H+ activity reversibly by 43 +/- 4% (N = 26) when the exchanger was activated by cellular acidification [21].
  • 4. These results indicate the importance of an intact sympathetic nervous system in the renal response to i.c.v. moxonidine [22].

Associations of Physiotens with other chemical compounds


Gene context of Physiotens

  • Inhibition or depletion of PKC blocked activation of ERK by moxonidine [19].
  • We conclude that the new I1-imidazoline receptor agonist moxonidine stimulates GH release to a similar extent as clonidine [27].
  • Moxonidine and NGF both increased levels of MKP-2 by three-fold [28].
  • The aim of this study was to evaluate the effect of a new antihypertensive agent, moxonidine (M), on microalbuminuria (urine albumin excretion, UAE), plasma thrombomodulin (TM), and tissue plasminogen activator inhibitor (PAI-1) in patients with mild to moderate EH associated with increased UAE [29].
  • After irreversible blockade of alpha2-adrenergic receptors, binding was inhibited by the selective I1-agonist, moxonidine, and the I1-antagonist, efaroxan, in a concentration-dependent (10-12 to 10-5 M) manner [30].

Analytical, diagnostic and therapeutic context of Physiotens


  1. Metabolic and hemodynamic effects of moxonidine in the Zucker diabetic fatty rat model of type 2 diabetes. Yakubu-Madus, F.E., Johnson, W.T., Zimmerman, K.M., Dananberg, J., Steinberg, M.I. Diabetes (1999) [Pubmed]
  2. The effects of moxonidine, a novel imidazoline, on plasma norepinephrine in patients with congestive heart failure. Moxonidine Investigators. Swedberg, K., Bergh, C.H., Dickstein, K., McNay, J., Steinberg, M. J. Am. Coll. Cardiol. (2000) [Pubmed]
  3. Lowering of microalbuminuria in diabetic patients by a sympathicoplegic agent: novel approach to prevent progression of diabetic nephropathy? Strojek, K., Grzeszczak, W., Górska, J., Leschinger, M.I., Ritz, E. J. Am. Soc. Nephrol. (2001) [Pubmed]
  4. Chronic I(1)-imidazoline agonism : sympathetic mechanisms in hypertension. Greenwood, J.P., Scott, E.M., Stoker, J.B., Mary, D.A. Hypertension (2000) [Pubmed]
  5. Relative importance of central imidazoline receptors for the antihypertensive effects of moxonidine and rilmenidine. Chan, C.K., Head, G.A. J. Hypertens. (1996) [Pubmed]
  6. Non-adrenergic exploratory behavior induced by moxonidine at mildly hypotensive doses. Zhu, H., Paul, I.A., Stec, D.E., Peeler, D.F., Piletz, J.E. Brain Res. (2003) [Pubmed]
  7. Central moxonidine on water and NaCl intake. Menani, J.V., Sato, M.A., Haikel, L., Vieira, A.A., de Andrade, C.A., da Silva, D.C., Renzi, A., De Luca, L.A. Brain Res. Bull. (1999) [Pubmed]
  8. Heterozygous alpha 2A-adrenergic receptor mice unveil unique therapeutic benefits of partial agonists. Tan, C.M., Wilson, M.H., MacMillan, L.B., Kobilka, B.K., Limbird, L.E. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  9. Effects of low dose sympathetic inhibition on glomerulosclerosis and albuminuria in subtotally nephrectomized rats. Amann, K., Rump, L.C., Simonaviciene, A., Oberhauser, V., Wessels, S., Orth, S.R., Gross, M.L., Koch, A., Bielenberg, G.W., Van Kats, J.P., Ehmke, H., Mall, G., Ritz, E. J. Am. Soc. Nephrol. (2000) [Pubmed]
  10. [125I]2-(2-chloro-4-iodo-phenylamino)-5-methyl-pyrroline (LNP 911), a high-affinity radioligand selective for I1 imidazoline receptors. Greney, H., Urosevic, D., Schann, S., Dupuy, L., Bruban, V., Ehrhardt, J.D., Bousquet, P., Dontenwill, M. Mol. Pharmacol. (2002) [Pubmed]
  11. Moxonidine. A review of its pharmacology, and therapeutic use in essential hypertension. Chrisp, P., Faulds, D. Drugs (1992) [Pubmed]
  12. Placebo-controlled comparison of the efficacy and tolerability of once-daily moxonidine and enalapril in mild-to-moderate essential hypertension. Küppers, H.E., Jäger, B.A., Luszick, J.H., Gräve, M.A., Hughes, P.R., Kaan, E.C. J. Hypertens. (1997) [Pubmed]
  13. Pharmacological therapy can increase capillary density in post-infarction remodeled rat hearts. Van Kerckhoven, R., van Veghel, R., Saxena, P.R., Schoemaker, R.G. Cardiovasc. Res. (2004) [Pubmed]
  14. Moxonidine treatment of hypertensive patients with advanced renal failure. Vonend, O., Marsalek, P., Russ, H., Wulkow, R., Oberhauser, V., Rump, L.C. J. Hypertens. (2003) [Pubmed]
  15. Mechanisms of antihyperglycemic effects of moxonidine in the obese spontaneously hypertensive Koletsky rat (SHROB). Ernsberger, P., Ishizuka, T., Liu, S., Farrell, C.J., Bedol, D., Koletsky, R.J., Friedman, J.E. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  16. Atrial natriuretic peptide is involved in renal actions of moxonidine. Mukaddam-Daher, S., Gutkowska, J. Hypertension (2000) [Pubmed]
  17. Antihypertensive agent moxonidine enhances muscle glucose transport in insulin-resistant rats. Henriksen, E.J., Jacob, S., Fogt, D.L., Youngblood, E.B., Gödicke, J. Hypertension (1997) [Pubmed]
  18. Coupling of I1-imidazoline receptors to diacylglyceride accumulation in PC12 rat pheochromocytoma cells. Separovic, D., Kester, M., Ernsberger, P. Mol. Pharmacol. (1996) [Pubmed]
  19. The I1-imidazoline receptor in PC12 pheochromocytoma cells activates protein kinases C, extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK). Edwards, L., Fishman, D., Horowitz, P., Bourbon, N., Kester, M., Ernsberger, P. J. Neurochem. (2001) [Pubmed]
  20. Identification of IRAS/Nischarin as an I(1)-imidazoline receptor in PC12 rat pheochromocytoma cells. Sun, Z., Chang, C.H., Ernsberger, P. J. Neurochem. (2007) [Pubmed]
  21. Moxonidine inhibits Na+/H+ exchange in proximal tubule cells and cortical collecting duct. Schlatter, E., Ankorina-Stark, I., Haxelmans, S., Hohage, H. Kidney Int. (1997) [Pubmed]
  22. The role of the peripheral sympathetic nervous system in the natriuresis following central administration of an I1 imidazoline agonist, moxonidine. Penner, S.B., Smyth, D.D. Br. J. Pharmacol. (1995) [Pubmed]
  23. Lack of pharmacokinetic interactions between moxonidine and digoxin. Pabst, G., Weimann, H.J., Weber, W. Clinical pharmacokinetics. (1992) [Pubmed]
  24. Non-adrenergic inhibition at prejunctional sites by agmatine of purinergic vasoconstriction in rabbit saphenous artery. Zhao, D., Ren, L.M. Neuropharmacology (2005) [Pubmed]
  25. Attenuated renal response to moxonidine and rilmenidine in one kidney-one clip hypertensive rats. Li, P., Penner, S.B., Smyth, D.D. Br. J. Pharmacol. (1994) [Pubmed]
  26. The role of I(1)-imidazoline and alpha(2)-adrenergic receptors in the modulation of glucose metabolism in the spontaneously hypertensive obese rat model of metabolic syndrome X. Velliquette, R.A., Ernsberger, P. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  27. Growth hormone secretion in response to the new centrally acting antihypertensive agent moxonidine in normal human subjects: comparison to clonidine and GHRH. Bamberger, C.M., Mönig, H., Mill, G., Gödde, E., Schulte, H.M. Exp. Clin. Endocrinol. Diabetes (1995) [Pubmed]
  28. The I(1)-imidazoline receptor in PC12 pheochromocytoma cells reverses NGF-induced ERK activation and induces MKP-2 phosphatase. Edwards, L., Ernsberger, P. Brain Res. (2003) [Pubmed]
  29. Moxonidine effect on microalbuminuria, thrombomodulin, and plasminogen activator inhibitor-1 levels in patients with essential hypertension. Krespi, P.G., Makris, T.K., Hatzizacharias, A.N., Triposkiadis, P., Tsoukala, C., Kyriaki, D., Votteas, V., Kyriakidis, M. Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy. (1998) [Pubmed]
  30. Imidazoline receptors in the heart: characterization, distribution, and regulation. El-Ayoubi, R., Gutkowska, J., Regunathan, S., Mukaddam-Daher, S. J. Cardiovasc. Pharmacol. (2002) [Pubmed]
  31. Safety and tolerability of moxonidine in the treatment of hypertension. Schachter, M., Luszick, J., Jäger, B., Verboom, C., Söhlke, E. Drug safety : an international journal of medical toxicology and drug experience. (1998) [Pubmed]
  32. Prototypical imidazoline-1 receptor ligand moxonidine activates alpha2-adrenoceptors in bulbospinal neurons of the RVL. Hayar, A., Guyenet, P.G. J. Neurophysiol. (2000) [Pubmed]
  33. Effects of sympathetic inhibition on exertional dyspnoea, ventilatory and metabolic responses to exercise in normotensive humans. Galloway, S.D., De Vito, G., McClure, S., Nimmo, M.A., McMurray, J.J. Clin. Sci. (2000) [Pubmed]
  34. Metabolism and disposition of the antihypertensive agent moxonidine in humans. He, M.M., Abraham, T.L., Lindsay, T.J., Schaefer, H.C., Pouliquen, I.J., Payne, C., Czeskis, B., Shipley, L.A., Oliver, S.D., Mitchell, M.I. Drug Metab. Dispos. (2003) [Pubmed]
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