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Chemical Compound Review

Norepinephrine, (+)-Isomer     4-(2-amino-1-hydroxy- ethyl)benzene-1,2-diol

Synonyms: Noradrop, d-Arterenol, dl-Arterenol, SureCN2610, AG-C-58215, ...
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Disease relevance of noradrenaline

  • Rats injected i.p. with LPS (0.5 for 4 consecutive days became tolerant to an i.v. injection of LPS (2 in that both hypotension and vascular hyporeactivity to NE were significantly attenuated [1].
  • CONCLUSIONS: An increase of NE levels may result in inhibition of syncope and an EP surge may be a triggering mechanism for neurally mediated syncope [2].
  • These observations suggest that altered E, as opposed to NE, may represent an early defect of the sympathoadrenal system in diabetes mellitus [3].
  • To study the effects of CLON on stimulated NE and E secretion, six normal men received a single dose of CLON followed by induction of hypoglycemia with insulin [4].
  • The data are compatible with inhibitory effects of NE in the cortex and suggest a potential of alpha 1-adrenergic blockage in development of novel therapeutic approaches to brain injury [5].

Psychiatry related information on noradrenaline

  • Reduced brain 5-HT and elevated NE turnover and metabolites in bipolar affective disorder [6].
  • It is suggested that feeding behavior is stimulated by low levels of CLON and decreased by further production of norepinephrine (NE), and FA may play the disturbance of sleeping and then enhance food intake [7].
  • Maternal deprivation induced a significant increase in basal plasma NE concentration, which was greater in lesioned rats, and cardiac beta-adrenoreceptor density was decreased in lesioned rats [8].

High impact information on noradrenaline


Chemical compound and disease context of noradrenaline

  • When patients experienced syncope during tilting with ISP, a significant 5.0-fold increase in EP at syncope was registered concomitant with a small 1.7-fold increase in NE [2].
  • We studied whether diabetes mellitus affects the bradykinin (BK)-induced release of norepinephrine (NE) from rat cardiac sympathetic endings in situ [13].
  • Taken together, these data show that when low numbers of E. coli are inoculated into SAPI+serum, NE, DBS, and related catecholamines induce the enterobactin iron uptake system [14].
  • Moreover, after growth in an iron-limited M9 medium in the absence of NE, ethyl acetate extracts of the E. coli entA(+) parent but not of the entA mutant contained AI, i.e., stimulated the growth of E. coli in SAPI+serum [14].
  • Using a variety of NE precursors, metabolites, and therapeutic agents, we demonstrated that their ability to stimulate E. coli growth in SAPI+serum is dependent on the presence of a catechol (1,2-dihydroxybenzene) moiety with maximal activity requiring a two-carbon substituent incorporating a terminal primary amine [14].

Biological context of noradrenaline

  • Those who required noradrenaline (NA) for blood pressure support had a significantly lower increment (median, 161 vs. 540 nmol/L; P <.001) following synacthen compared with patients who did not [15].
  • In the DALD group, NA decreased forearm blood flow by 21.0 +/- 6.2% and increased vascular resistance by 37.2 +/- 12.3%, whereas respective changes in the CALD group were 41.8 +/- 6.2% (P < .01) and 77.8 +/- 9.9% (P < .02) [16].
  • CONCLUSION: Exaggerated NE responses and heart rate increases, as well as delayed ACTH release, were observed among female FM patients compared with age-matched female controls [17].
  • Insulin significantly attenuated NE-induced vasoconstriction in NC but not in HC (P<0.01) [18].
  • Peripheral venous pressure declined from 107 to 77 mm H2O; this decrease correlated with the change in NE levels [19].

Anatomical context of noradrenaline


Associations of noradrenaline with other chemical compounds

  • The renal vasoconstrictor effect of AVP, AII, and NE produced in the presence of Ca2+ was not additive and remained unaltered when given together with BK.(ABSTRACT TRUNCATED AT 250 WORDS)[23]
  • We also discuss the known mechanisms involved in the regulation of BNST NA extracellular levels and the possible interactions between NA and corticotropin-releasing hormone (CRH), and of CRH with glutamate (GLU) in the regulation of the HPA axis activity exerted by the BNST [24].
  • Desipramine (DMI), a tricyclic antidepressant and norepinephrine (NE) reuptake blocker, is reported to induce ACTH and cortisol release acutely in humans, probably by facilitating central NE neurotransmission [20].
  • In cremaster arterioles, the contribution of a myogenic component to the constriction on intravenous infusion of norepinephrine (NE) or angiotensin II (Ang II) was studied [25].
  • DMP administration before exercise caused a significant increase in plasma PRL (P = 0.0009), a greater increase in plasma NE at the end of the exercise (P = 0.002), and an overall increase in plasma E (P = 0.02) and FFA (P = 0.02) concentrations [26].

Gene context of noradrenaline

  • In victim mice recuperating after 1 week of daily stress, EPI levels and PNMT activities were back to normal after 4 days whereas NE levels and TH activities returned to normal only after 1 week [27].
  • Cold exposure, which is known to stimulate NE release from sympathetic nerve terminals in BAT, led to a significant increase in eNOS mRNA in this tissue [28].
  • We have recently observed that NE neurons in the human locus coeruleus (LC) express moderate levels of both ER transcripts [29].
  • Consistent with this hypothesis, E. coli strains with mutations in ferrienterobactin transport (fepA or tonB) or enterobactin biosynthesis (entA) did not respond to NE [14].
  • 1. Experiments were designed to investigate the effects of the inducible nitric oxide synthase (iNOS) stimulator, lipopolysaccharide (LPS), on noradrenaline (NA) responses and on NOS activity and its expression in intact mesenteric resistance arteries (MRAs) from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats [30].

Analytical, diagnostic and therapeutic context of noradrenaline


  1. Attenuation of the induction of nitric oxide synthase by endogenous glucocorticoids accounts for endotoxin tolerance in vivo. Szabó, C., Thiemermann, C., Wu, C.C., Perretti, M., Vane, J.R. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  2. Triggering mechanism for neurally mediated syncope induced by head-up tilt test: role of catecholamines and response to propranolol. Kikushima, S., Kobayashi, Y., Nakagawa, H., Katagiri, T. J. Am. Coll. Cardiol. (1999) [Pubmed]
  3. Plasma epinephrine disturbances in diabetic subjects during standing and after isometric exercise. Gustafson, A.B., Kalkhoff, R.K. J. Clin. Endocrinol. Metab. (1981) [Pubmed]
  4. Effects of clonidine on hormone and substrate responses to hypoglycemia. Metz, S.A., Halter, J.B. Clin. Pharmacol. Ther. (1980) [Pubmed]
  5. The effect of alpha-adrenergic receptor blockers prazosin and yohimbine on cerebral metabolism and biogenic amine content of traumatized brain. Inoue, M., McHugh, M., Pappius, H.M. J. Cereb. Blood Flow Metab. (1991) [Pubmed]
  6. Reduced brain 5-HT and elevated NE turnover and metabolites in bipolar affective disorder. Young, L.T., Warsh, J.J., Kish, S.J., Shannak, K., Hornykeiwicz, O. Biol. Psychiatry (1994) [Pubmed]
  7. Induction of food intake by a noradrenergic system using clonidine and fusaric acid in the neonatal chick. Bungo, T., Shimojo, M., Masuda, Y., Choi, Y.H., Denbow, D.M., Furuse, M. Brain Res. (1999) [Pubmed]
  8. The role of the anterodorsal thalami nuclei in the regulation of adrenal medullary function, beta-adrenergic cardiac receptors and anxiety responses in maternally deprived rats under stressful conditions. Suárez, M.M., Rivarola, M.A., Molina, S.M., Levin, G.M., Enders, J., Paglini, P. Stress (Amsterdam, Netherlands) (2004) [Pubmed]
  9. Plasma l-[3H]norepinephrine, d-[14C]norepinephrine, and d,l-[3H]isoproterenol kinetics in essential hypertension. Goldstein, D.S., Horwitz, D., Keiser, H.R., Polinsky, R.J., Kopin, I.J. J. Clin. Invest. (1983) [Pubmed]
  10. Localization and characterization of carbohydrates in adrenal medullary cells. Cantin, M., Benchimol, S. J. Cell Biol. (1975) [Pubmed]
  11. Neurohumoral prediction of benefit from carvedilol in ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group. Richards, A.M., Doughty, R., Nicholls, M.G., Macmahon, S., Ikram, H., Sharpe, N., Espiner, E.A., Frampton, C., Yandle, T.G. Circulation (1999) [Pubmed]
  12. Sympatholytic action of intravenous amiodarone in the rat heart. Du, X.J., Esler, M.D., Dart, A.M. Circulation (1995) [Pubmed]
  13. Augmented sympathetic response to bradykinin in the diabetic heart before autonomic denervation. Pietrzyk, Z., Vogel, S., Dietze, G.J., Rabito, S.F. Hypertension (2000) [Pubmed]
  14. The growth response of Escherichia coli to neurotransmitters and related catecholamine drugs requires a functional enterobactin biosynthesis and uptake system. Burton, C.L., Chhabra, S.R., Swift, S., Baldwin, T.J., Withers, H., Hill, S.J., Williams, P. Infect. Immun. (2002) [Pubmed]
  15. The clinical importance of adrenal insufficiency in acute hepatic dysfunction. Harry, R., Auzinger, G., Wendon, J. Hepatology (2002) [Pubmed]
  16. Inhibition of nitric oxide synthesis in the forearm arterial bed of patients with advanced cirrhosis. Campillo, B., Chabrier, P.E., Pelle, G., Sediame, S., Atlan, G., Fouet, P., Adnot, S. Hepatology (1995) [Pubmed]
  17. Responses of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis to interleukin-6: a pilot study in fibromyalgia. Torpy, D.J., Papanicolaou, D.A., Lotsikas, A.J., Wilder, R.L., Chrousos, G.P., Pillemer, S.R. Arthritis Rheum. (2000) [Pubmed]
  18. Insulin-mediated venodilation is impaired in patients with high cholesterol. Sung, B.H., Ching, M., Izzo, J., Dandona, P., Wilson, M.F. Hypertension (1998) [Pubmed]
  19. Effects of captopril on arterial and venous pressure, renal function, and humoral factors in severe chronic congestive heart failure. Kubo, S., Nishioka, A., Nishimura, H., Kawamura, K., Takatsu, T. Clin. Pharmacol. Ther. (1984) [Pubmed]
  20. The effect of desipramine on basal and naloxone-stimulated cortisol secretion in humans: interaction of two drugs acting on noradrenergic control of adrenocorticotropin secretion. Torpy, D.J., Grice, J.E., Hockings, G.I., Crosbie, G.V., Walters, M.M., Jackson, R.V. J. Clin. Endocrinol. Metab. (1995) [Pubmed]
  21. Effects of captopril on vascular noradrenergic transmission in SHR. Eikenburg, D.C. Hypertension (1984) [Pubmed]
  22. The effect of propranolol on catecholamine clearance. Ziegler, M.G., Chernow, B., Woodson, L.C., Coyle, J., Cruess, D., Lake, C.R. Clin. Pharmacol. Ther. (1986) [Pubmed]
  23. Evidence that bradykinin stimulates renal prostaglandin synthesis by a mechanism distinct from that of other vasoactive substances. Cooper, C.L., Malik, K.U. Circ. Res. (1987) [Pubmed]
  24. Role of noradrenergic projections to the bed nucleus of the stria terminalis in the regulation of the hypothalamic-pituitary-adrenal axis. Forray, M.I., Gysling, K. Brain Res. Brain Res. Rev. (2004) [Pubmed]
  25. Nitric oxide opposes myogenic pressure responses predominantly in large arterioles in vivo. de Wit, C., Jahrbeck, B., Schäfer, C., Bolz, S.S., Pohl, U. Hypertension (1998) [Pubmed]
  26. Endogenous dopamine (DA) and DA2 receptors: a mechanism limiting excessive sympathetic-adrenal discharge in humans. Mannelli, M., Pupilli, C., Fabbri, G., Musante, R., De Feo, M.L., Franchi, F., Giusti, G. J. Clin. Endocrinol. Metab. (1988) [Pubmed]
  27. Alterations of mouse adrenal medullary catecholamines and enzymes in response to attack: effect of pre- and post-treatment with phenobarbital. Thoa, N.B., Tizabi, Y., Kopin, I.J., Maengwyn-Davies, G.D. Psychopharmacology (Berl.) (1976) [Pubmed]
  28. Enhanced gene expression of endothelial nitric oxide synthase in brown adipose tissue during cold exposure. Kikuchi-Utsumi, K., Gao, B., Ohinata, H., Hashimoto, M., Yamamoto, N., Kuroshima, A. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2002) [Pubmed]
  29. Estrogen receptor gene expression in relation to neuropsychiatric disorders. Ostlund, H., Keller, E., Hurd, Y.L. Ann. N. Y. Acad. Sci. (2003) [Pubmed]
  30. Influence of hypertension on nitric oxide synthase expression and vascular effects of lipopolysaccharide in rat mesenteric arteries. Briones, A.M., Alonso, M.J., Marín, J., Balfagón, G., Salaices, M. Br. J. Pharmacol. (2000) [Pubmed]
  31. Acceleration of stiffness in underperfused diabetic rat hearts by glyburide, a KATP channel blocker, and its prevention by levcromakalim and insulin. Higuchi, M., Miyagi, K., Kayo, S., Sakanashi, M. Cardiovasc. Res. (1997) [Pubmed]
  32. Synthesis, internalization, and localization of atrial natriuretic peptide in rat adrenal medulla. Morel, G., Chabot, J.G., Garcia-Caballero, T., Gossard, F., Dihl, F., Belles-Isles, M., Heisler, S. Endocrinology (1988) [Pubmed]
  33. R-fluoxetine increases extracellular DA, NE, as well as 5-HT in rat prefrontal cortex and hypothalamus: an in vivo microdialysis and receptor binding study. Koch, S., Perry, K.W., Nelson, D.L., Conway, R.G., Threlkeld, P.G., Bymaster, F.P. Neuropsychopharmacology (2002) [Pubmed]
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