Disease relevance of NORMETANEPHRINE

• CONCLUSIONS: Measurements of plasma normetanephrine and metanephrine are useful in screening for pheochromocytomas in patients with a familial predisposition to these tumors [1].
• One patient with von Hippel-Lindau disease had a normal plasma normetanephrine concentration; this patient had a very small adrenal tumor (<1 cm) [1].
• Plasma normetanephrine and metanephrine for detecting pheochromocytoma in von Hippel-Lindau disease and multiple endocrine neoplasia type 2 [1].
• The concentrations of free and total normetanephrine (NMN) were determined in the plasma of normotensives and patients with primary hypertension and pheochromocytoma [2].
• MEN 2 patients all had elevated plasma concentrations of the epinephrine metabolite, metanephrine, whereas VHL patients showed specific increases in the norepinephrine metabolite, normetanephrine [3].

Psychiatry related information on NORMETANEPHRINE

• The method is applicable to the relatively low amounts of normetanephrine (100-600 micrograms/24 h) and metanephrine (50-400 micrograms/24 h) found in normal subjects and patients with depressive disorders or hypertension [4].
• Psychosocial factors accounted for 37% of the link between MS and normetanephrine output, and 7% to 19% for CAA [5].
• Urinary excretion of the norepinephrine metabolites 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and normetanephrine (NMR) was measured in Tourette's Syndrome (TS) patients and in control subjects matched for age and education [6].

High impact information on NORMETANEPHRINE

• The cremaster skeletal muscle of anesthetized rats was acutely denervated and suspended in a Krebs bath containing cocaine, normetanephrine, and propranolol to block uptake1, uptake2, and beta-receptors, respectively [7].
• The uptake and storage of 3H-norepinephrine by neural crest cultures containing CA+ cells were inhibited in the presence of desmethylimipramine and by incubation at 0 degrees C, but were unaffected by normetanephrine [8].
• Compounds devoid of significant alpha-adrenergic activity, such as pyrocatechol, 3,4-dihydroxymandelic acid, normetanephrine, and D-lysergic acid, did not effectively compete for [3H]dihydroergocryptine binding sites [9].
• In combination with I-MIBG scintigraphy, platelet norepinephrine had a sensitivity of 100%, plasma norepinephrine/MIBG of 97.1%, total urine normetanephrine/MIBG of 96.6%, and urine norepinephrine/MIBG of 95.3% [10].
• CONCLUSIONS: The authors propose the hypothesis that drugs or other agents that increase levels of normetanephrine or otherwise inhibit the extraneuronal monoamine transporter, uptake 2, in the brain will speed up the clinical effects of norepinephrine reuptake inhibitor antidepressant drugs [11].

Chemical compound and disease context of NORMETANEPHRINE

• CONCLUSIONS: The tests of choice to establish the diagnosis of pheochromocytoma are urinary normetanephrine and platelet norepinephrine [10].
• Measurements of plasma-free normetanephrine and metanephrine provide a sensitive test for diagnosis of pheochromocytoma but may fail to detect tumors that produce predominantly dopamine [12].
• Tissue concentrations of dihydroxyphenylalanine, metanephrine, normetanephrine, vanillylmandelic acid, and 3-methoxy-4-hydroxyphenylethylglycol were determined in 29 normal adrenal medullas, 13 benign pheochromocytomas and 6 malignant pheochromocytomas, respectively [13].
• The values for subjects with pheochromocytoma varied from 1.5 to 27.5 (mean = 9.9) microgram/mg creatinine for NMN and 0.10 to 1.60 (mean = 0.86) microgram/mg creatine for MN [14].
• One patient, a 21-year-old woman taking mesalamine for ulcerative colitis, had a remarkably elevated urinary normetanephrine level, which resulted in the initial misdiagnosis of a 10-cm right adrenal incidentaloma as a pheochromocytoma [15].

Biological context of NORMETANEPHRINE

• The disproportionate decrease in excretion of normetanephrine by patients with MSA is consistent with observations in experimental animals that O-methylation is the primary metabolic route for active released norepinephrine, whereas deamination is the predominant metabolic route for intraneuronal degradation of the catecholamine [16].
• Plasma NMN (r = 0.27; P = 0.02) but not MN positively correlated with age, whereas only plasma catecholamines (and not metanephrines) were positively correlated (P <0.05) with diastolic blood pressure [17].
• In this method for measuring metanephrine and normetanephrine in urine, they are freed from their conjugates by hydrolysis in acid, neutralized, and isolated on a cation-exchange resin [18].
• The level of the initial methylation product, normetanephrine, also showed a biphasic decline, which did not correspond to that of [3H]noradrenaline but rather was faster throughout the experiment [19].
• 4. NA (10(-2) M by pressure ejection) did not alter membrane potential even in the presence of NMN and DMI (each 10(-6) M) [20].

Anatomical context of NORMETANEPHRINE

• Compounds such as dihydroxyphenylaline, dihydroxymandelic acid, normetanephrine, pyrocatechol, and phentolamine which are structurally related to beta-adrenergic agents, but are devoid of beta-adrenergic physiologicl effects in adipocytes, did not compete for the binding sites [21].
• Conjugated normetanephrine in human and rat plasma and erythrocytes [22].
• Microinjection of opioids into the nucleus reticularis gigantocellularis of the rat: analgesia and increase in the normetanephrine level in the spinal cord [23].
• In this group the meningeal cells were unaffected by the treatment, and the morphology of the dentate gyrus was normal 30 days p.i. of 6-OHDA plus NMN [24].
• We postulate that the higher urinary outputs of norepinephrine and its metabolite, normetanephrine, reflect dysregulation of the sympathetic nervous system in depression [25].

Associations of NORMETANEPHRINE with other chemical compounds

• We describe a procedure for the direct measurement of metanephrine (MN) and normetanephrine (NMN) in hydrolyzed urine, using HPLC with coulometric array detection [26].
• We normalized values for urinary 24-h excretion of metanephrine, normetanephrine, and 3-methoxytyramine by dividing by an age- and sex-specific reference range [27].
• Children with ADHD alone had lower NE/NMN and EPI/metanephrine ratios compared to controls [28].
• Children with TBI and ADHD excreted significantly more normetanephrine in resting situations and less epinephrine (EPI) after cognitive stress, and showed a decreased blink rate compared to normal controls [29].
• The Ki values calculated by Marquardt non-linear least squares regression analysis and Hunter-Downs method, respectively, were normetanephrine: 2.75 microM and 3.47 microM, and corticosterone: 1.52 microM and 1.44 microM [30].

Gene context of NORMETANEPHRINE

• The excretion of normetanephrine, a marker for sympathetic nervous activity, was reduced during ST in COX-1(+/+) (6.9+/-0.9 versus 3.2+/-0.6 g . g(-1) creatinine . 10(-3); P<0.01) [31].
• Normetanephrine, the COMT-dependent metabolite of NE, was formed in large quantities during post-uptake incubation [32].
• The trauma patients differed from the elective neurosurgery patients with regard to D-dimer levels, PT, PTT, protein C levels, and urinary normetanephrine concentrations [33].
• 4. Both clorgyline (a selective MAO-A inhibitor) and selegiline (a selective MAO-B inhibitor) reduced the formation of dihydroxyphenylglycol (DOPEG), DOMA and O-methylated-deaminated metabolites (OMDA), and increased that of normetanephrine (NMN) [34].
• A cytosol fraction of chorio-decidua was incubated with [14C]-S-adenosyl-L-methionine and normetanephrine for 60 min to measure PNMT activity [35].

Analytical, diagnostic and therapeutic context of NORMETANEPHRINE

• Urinary normetanephrine and metanephrine measured by radioimmunoassay for the diagnosis of pheochromocytoma: utility of 24-hour and random 1-hour urine determinations [36].
• At 4 weeks, plasma levels of NE and DOPEG were lower (p less than 0.01), whereas levels of DOMA and NMN were higher (p less than 0.02 and p less than 0.001, respectively) in the 1K1C group than the control group [37].
• We report the use of liquid chromatography with electrochemical detection to determine plasma concentrations of normetanephrine (NMN) and metanephrine (MN) [38].
• Evaluation of urinary metanephrine and normetanephrine enzyme immunoassay (ELISA) kits by comparison with isotope dilution mass spectrometry [39].
• Elevation of daytime norepinephrine and normetanephrine with return to control levels following tracheostomy implies increased sympathetic activity throughout the day [40].

References