Normetanephrine

Non-n uronaJ uptake inhibiters ( Uptake 1 ) Corticosteroids Normetanephrine (NMN)... 

The figure below illustrates proposed sites of action of drugs. Tor each drug listedt select the site of action that the drug is most likely to inhibit (a, a receptor iT J3 receptor COMTt cat e cho l-O-methyl transferase MAOt monoamine oxidase NET norepinephrine NMNt normetanephrine). 

Fio. 51. Dependence of retention of catecholamines on volume percent acetonitrile in hetaeric chromatography. The ehient is water-acetonitrile at the volume percent indicated containing 0.2% (v/v) sulfuric acid and 0.1% (w/v) sodium dodecyl sulfote. The catecholamines separated are noradrenaline (NA), adrenaline (A). L-3,4-dihydroxyphenylalanine (LD), normetanephrine (NMA), dopamine (DA), metadrenaline (MA), and 3-methoxytyramine (MDA). Column 5- tm octadecyl silica treated with triroethylchlorosilane, 125 X 5 mm i.d. Reprinted with permission from Knox and Jurand (223). ... 

Carlsson, A., Lindquist, M. Effect of chloipromazine or haloperidol on formation of 3-methoxvtrvptamine and normetanephrine. Acta Pharmacol. (Kohenhavn) 20, 140-144, 1963. ... 

This reaction is catalysed by enzyme methyl-transferases (catechol-o-methyl-transferase) and generally uses S-adenosylmethionine as a methyl donor. Examples are conversion of norepi-nephrine into normetanephrine, which has less than one percent of the vasoconstrictor activity of the parent compound. 

Pheochromocytoma is a tumor of the adrenal medulla or sympathetic ganglion cells. The tumor secretes catecholamines, especially norepinephrine and epinephrine. The patient in the case study at the beginning of the chapter had a left adrenal pheochromocytoma that was identified by imaging. In addition, she had elevated plasma and urinary norepinephrine, epinephrine, and their metabolites, normetanephrine and metanephrine. 

In old rats (26 months old), oral administration of EGb (10 mg/kg and 30 mg/kg, for 7 days) produces elevations of 5-HT in the frontal cortex, hippocampus, striatum and hypothalamus, and of dopamine levels in the hippocampus and hypothalamus compared with controls. On the other hand, EGb decreases the 5-HT level in the pons, and those of norepinephrine in the hippocampus and hypothalamus [157]. In this connection, Racagni et al. [158] showed that the O-methylated amine metabolite of norepinephrine, normetanephrine, was markedly elevated (+500%) in the cerebral cortex by chronic oral administration of EGb (100 mg/kg, for 14 days), suggesting an increase of norepinephrine turnover. In addition, treatment with EGb (50 or 100 mg/kg/day, for 20 days) diminished the increased plasma levels of epinephrine, norepinephrine, and corticosterone induced by acute auditory stress in young and old rats [113]. 

Oxidation of fi-(4-Hydroxy-3-methoxyphenyl)ethylamines The j3-(4-hydroxy-3-methoxyphenyl)ethylamines [i.e. the catecholamine 03-methyl ethers, metanephrine (18) and normetanephrine (19)] are known to be among the major in vivo metabolites of... 

The mechanisms of these interesting oxidations require further study, and attempts should be made to isolate the intermediate aminochromes (or a simple derivative, such as the semicarbazone). However, it is difficult to escape the conclusion that aminochromes can be readily obtained by the oxidation of compounds such as metanephrine and normetanephrine. 

A sensitive spectrophotometric method based on the strong absorption of the aminochrome-sodium bisulfite addition products (see Section IV, F) at ca. 350 m/x. has been described recently by van Espen128and Oesterling and Tse 277-278 for determining total catecholamines. While not as sensitive as the fluorimetric procedures, this method is considerably more sensitive than the older colorimetric methods based on the visible absorption peak of the aminochromes. Also, it does not have many of the disadvantages (e.g. costly equipment and unstable blanks) often associated with fluorimetric techniques. The basic procedure can be satisfactorily applied to the differential determination of mixtures of adrenaline, noradrenaline, dopamine, metanephrine, and normetanephrine.178... 

Degradation of catecholamines The catecholamines are inacti vated by oxidative deamination catalyzed by monoamine oxidase (MAO), and by O-methylation carried out by catechol-O-methyl-transferase (COMT, Figure 21.15). The two reactions can occur in either order. The aldehyde products of the MAO reaction are axi dized to the corresponding acids. The metabolic products of these reactions are excreted in the urine as vanillylmandelic acid, metanephrine, and normetanephrine. 

Fales and Pisano (30) were the first to describe the gas chromatographic analysis of amphetamine. They used 4% SE-30 in a silanized glass column and an argon ionization detector for the separation of (3-phenethylamine, amphetamine, norephedrine, eph drine, histamine, tyramine, dimethyltriptamine, tryptamine, 5-methoxytryptamine, benzylamine, N-methylbenzylamine, octopamine, synephrine, normetanephrine, serotonin, N-acetyltryptamine, find melatonin. The method was also used for the analysis of amphetamine extracted from urine. 

On-chip chiral separation of enantiomers of adrenaline, noradrenaline, and dopamine was achieved using a mixture of carboxymethyl-p-cyclodextrin (CMCD) and a polyamidoamine dendrimer (Starburst) [120], On-chip chiral separation of enantiomers of homovanillic acid, DOPA, cDOPA, methoxy-tyramine (MT), metanephrine, and normetanephrine was achieved using a mixture of 18-crown-6-ether and carboxymethyl-P-cyclodextrin [120],... 

The most abundant alkaloid in Coryphantha macromeris, normacromerine, has been shown to originate from tyrosine (330). Tyramine and JV-methyltyramine are efficiently incorporated into normacromerine while octopamine and dopamine are poor precursors. Norepinephrine, epinephrine, normetanephrine, and meta-nephrine have all been shown to be biosynthetically incorporated into normacromerine, and they have also been shown to be naturally occurring trace intermediates in this cactus species (331, 334). Normacromerine is only slowly converted to macromerine in C. macromeris (332). The results indicate that alternative pathways to normacromerine exist precise conclusions regarding the biosynthesis of normacromerine must await further studies. 

The most well known of the naturally occurring phenethylamine derivatives (Table I) are the transmitters of the sympathetic nervous system, epinephrine, norepinephrine, and dopamine. All these compounds are 3,4-dioxygenated in the aromatic nucleus and are collectively known as the catecholamines. Norepinephrine is the transmitter of most sympathetic postganglionic fibers, dopamine is the predominant transmitter of the mammalian extrapyramidal system and of several mesocortical and mesolimbic neuronal pathways, and epinephrine is the major hormone of the adrenal medulla (363). The literature that has accumulated on the action of these compounds in higher animals is enormous. Metanephrine and normetanephrine are known from animals as deactivated metabolites of epinephrine and norepinephrine that result from the action of the enzyme catechol O-methyltransferase (364). 

Potential fates of recaptured norepinephrine Once norepinephrine reenters the cytoplasm of the adrenergic neuron it may be taken up into adrenergic vesicles via the amine transporter system and be sequestered for release by another action potential or persist in a protected pool. Alternatively, norepinephrine can be oxidized by monoamine oxidase (MAO) present in neuronal mitochondria. The inactive products of norepinephrine metabolism are excreted in the urine as vanillylmandelic acid (VMA), metanephrine and normetanephrine. 

---