Catecholamines metabolism

Kopin IJ (1985) Catecholamine metabolism basic aspects and clinical significance. Pharmacol Rev 37(4) 333-364... 

Amantidine, bromocriptine, mazindol, pergolide, cabergoline, L-dopa/carbidopa, pramipexole, ABT-431, catecholamine metabolism inhibitors (disulfiram, phenelzine, selegiline), amineptine Methylphenidate, /-amphetamine, tropanes, GBR-12909 (partial agonist that may also act as antagonist), modafinil, coca tea... 

Taylor, KM and Laverty, R (1969) The effect of chlordiazepoxide, diazepam and nitrazepam on catecholamine metabolism in regions of the rat brain. Eur. J. Pharmacol. 8 296-301. 

Because LCEC had its initial impact in neurochemical analysis, it is not, surprising that many of the early enzyme-linked electrochemical methods are of neurologically important enzymes. Many of the enzymes involved in catecholamine metabolism have been determined by electrochemical means. Phenylalanine hydroxylase activity has been determined by el trochemicaUy monitoring the conversion of tetrahydro-biopterin to dihydrobiopterin Another monooxygenase, tyrosine hydroxylase, has been determined by detecting the DOPA produced by the enzymatic reaction Formation of DOPA has also been monitored electrochemically to determine the activity of L-aromatic amino acid decarboxylase Other enzymes involved in catecholamine metabolism which have been determined electrochemically include dopamine-p-hydroxylase phenylethanolamine-N-methyltransferase and catechol-O-methyltransferase . Electrochemical detection of DOPA has also been used to determine the activity of y-glutamyltranspeptidase The cytochrome P-450 enzyme system has been studied by observing the conversion of benzene to phenol and subsequently to hydroquinone and catechol... 

Mechanism of Action Lithium s pharmacologic mechanism of action is not well understood and probably involves multiple effects. Possibilities include altered ion transport, increased intraneuronal catecholamine metabolism, neuroprotection or increased brain-derived neurotrophic factor, inhibition of second messenger systems, and reprogramming of gene expression.29... 

Tolcapone (Tasmar) and entacapone (Comtan) are used only in conjunction with carbidopa/L-dopa to prevent the peripheral conversion of L-dopa to dopamine (increasing the area under the curve of L-dopa by approximately 35%). Thus, on time is increased by about 1 hour. These agents significantly decrease off time and decrease L-dopa requirements. Concomitant use of nonselective MAO inhibitors should be avoided to prevent inhibition of the pathways for normal catecholamine metabolism. 

Disulfoton exposure altered catecholamine levels in animals, and this hormonal imbalance may be associated with elevated acetylcholine levels (Brzezinski 1969, 1972, 1973 Brzezinski and Ludwicki 1973 Brzezinski and Rusiecki 1970 Wysocka-Paruszewska 1970, 1971). In these studies, acute dosing with disulfoton caused increases in urinary and plasma noradrenaline and adrenaline levels, accompanied by decreases of adrenaline in the adrenal glands, in rats. In addition, the major urinary metabolite of catecholamine metabolism, 4-hydroxy-3-methoxymandelic acid (HMMA), was recovered in the urine from rats given acute doses of disulfoton (Wysocka-Paruszewska 1970,... 

Urine catecholamines may also serve as biomarkers of disulfoton exposure. No human data are available to support this, but limited animal data provide some evidence of this. Disulfoton exposure caused a 173% and 313% increase in urinary noradrenaline and adrenaline levels in female rats, respectively, within 72 hours of exposure (Brzezinski 1969). The major metabolite of catecholamine metabolism, HMMA, was also detected in the urine from rats given acute doses of disulfoton (Wysocka-Paruszewska 1971). Because organophosphates other than disulfoton can cause an accumulation of acetylcholine at nerve synapses, these chemical compounds may also cause a release of catecholamines from the adrenals and the nervous system. In addition, increased blood and urine catecholamines can be associated with overstimulation of the adrenal medulla and/or the sympathetic neurons by excitement/stress or sympathomimetic drugs, and other chemical compounds such as reserpine, carbon tetrachloride, carbon disulfide, DDT, and monoamine oxidase inhibitors (MAO) inhibitors (Brzezinski 1969). For these reasons, a change in catecholamine levels is not a specific indicator of disulfoton exposure. 

Increased levels of urinary catecholamines may also be associated with accumulation of acetylcholine that resulted from acetylcholinesterase inhibition by disulfoton. No human data were located to support this, but limited animal data provide some evidence. Disulfoton exposure caused a 173% and 313% increase in urinary noradrenaline and adrenaline levels in rats, respectively, within 72 hours (Brzezinski 1969). The major metabolite of catecholamine metabolism, HMMA, was also detected in the urine from rats given acute doses of disulfoton (Wysocka-Paruszewska 1971). 

Conjugations can also be brought about by sulfotransferases (SULTs) and glutathi-one-S-transferases (GSTs), both of which exist in a number of isoenzymic forms. Amines and alcohols are sulfate acceptors and SULTs are important in steroid hormone and catecholamine metabolism and like the UGTs require the sulfate to be activated prior to its incorporation into the target molecule (Figure 6.32). In this case, sulfate is activated at the expense of two molecules of ATP to form the final sulfate carrier PAPS O -phosphoadenosine-S -phosphosulfate). 

Honma T. 1987. Alteration of catecholamine metabolism in rat brain produced by inhalation exposure to methyl bromide. Jpn J Ind Health 29 218-219. 

Bagdy G, Perenyi A, Frecska E, Seregi A, Fekete MI, Tothfalusi L, Magyar K, Bela A, Arato M. (1988). Effect of adjuvant reserpine treatment on catecholamine metabolism in schizophrenic patients under long-term neuroleptic treatment. J Neural Transm. 71(1) 73-78. 

Pharmacology Lithium alters sodium transport in nerve and muscle cells, and effects a shift toward intraneuronal catecholamine metabolism. The specific mechanism in mania is unknown, but it affects neurotransmitters associated with affective disorders. Its antimanic effects may be the result of increases in norepinephrine reuptake and increased serotonin receptor sensitivity. Pharmacokinetics ... 

From the observation that tics were exacerbated by stress, and because cerebrospinal fluid flndings suggested possible alterations in central nervous system catecholamine metabolism, Cohen and colleagues (1979) used clonidine in the treatment of TS in what was among the first theory-based treatments for the disorder. 

Poitou P, Bohuon C Catecholamine metabolism in the rat brain after short and long term hthium administration. J Neurochem 25 535-537, 1975 Pollack MH, Hammerness P Adjunctive yohimbine for treatment of refractory depression. Biol Psychiatry 33 220-221, 1993 Pollack MH, Rosenbaum JF Verapamil in the treatment of recurrent unipolar depression. Biol Psychiatry 22 779-782, 1987... 

B. Aminochrome Formation as a Possible Minor Pathway for Catecholamine Metabolism... 

Two important pathways for catecholamine metabolism are O-methylation by COMT, which is cytoplasmically localized, and oxidative deamination by the mitochondrial localized enzyme MAO. There are large amounts of MAO in tissues such as the liver and the heart which are responsible for the removal of most of the circulating monoamine, including some taken in from the diet. Tyramine is found in bigb concentrations in certain foods such as cheese, and in wine. Normally, this tyramine is deaminated in the liver. However, if MAO is inhibited, the tyramine may then be converted into octopamine [104-14-57] which may indirecdy cause release of NE from nerve terminals to cause hypertensive crisis. Thus MAO, which is rdatively nonspecific, plays an important role in the detoxification of pharmacologically active amines ingested from the diet. 

Eisenhofer G, Kopin IJ, Goldstein DS. Catecholamine metabolism a contemporary view with implications for physiology and medicine. Pharmacol Rev. 2004 56 331-349. 

A.G. Nasello and O.A. Ramirez, Brain catecholamines metabolism in offspring of amphetamine treated rats, Pharmacol. Biochem. Behav., 9(1) (1978) 17-20. 

Rapid inactivation Not only are the catecholamines metabolized by COMT postsynaptically and by MAO intraneuronally, but they are also metabolized in other tissues. For example, COMT is in the gut wall and MAO is in the liver and gut wall. Thus catecholamines have only a brief period of action when given parenterally, and are ineffective when administered orally because of inactivation. 

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