Determination of catecholamines and their 3-O-methylated metabolites in urine by mass fragmentography with use of deuterated internal standards.

Muskiet, Frits A. J.; Thomasson, C G; Gerding, Albert; Fremouw-Ottevangers, D C; Nagel, G.T.; Wolthers, B.G.

doi:10.1093/clinchem/25.3.453

Cited by 38 publications

(9 citation statements)

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“…This table shows that the DA turnover rate in the three patients agreed with that of the contro!. Further, these were within the normal range as measured by others (34). We noticed, however, a relatively reduced excretion of DOPAC in urine of the patients.…”

Section: Kinetics Ofda Metabolismsupporting

confidence: 88%

Kinetic Study of Catecholamine Metabolism in Hereditary Progressive Dystonia

Jong

Haan²,

Manson³

et al. 1989

Neuropediatrics

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Kinetics of catecholamine biosynthesis and metabolism have been examined in patients with hereditary progressive dystonia with marked diurnal fluctuation of symptoms (HPD, Segawa's disease). Three patients and a healthy control received an oral load of deuterated tyrosine, and monodeuterium labelled catecholamines and their metabolites in urine and plasma were examined by gas chromatography-mass spectrometry. Patients excreted normal amounts of the primary metabolites of dopamine (dihydroxyphenylacetic acid, homovanillic acid) in urine, suggesting normal rates of dopamine production. However, the biological half-life of dopamine in the patients was reduced to about half that of controls. Noradrenaline biosynthesis and metabolism were normal. Taken together, these results are interpreted to show a reduced biological half-life of dopamine in the brains of these patients, possibly caused by a defect in dopamine storage. Impaired dopamine storage may be the basis of the diurnal fluctuation in symptoms.

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Section: Kinetics Ofda Metabolismsupporting

confidence: 88%

Kinetic Study of Catecholamine Metabolism in Hereditary Progressive Dystonia

Jong

Haan²,

Manson³

et al. 1989

Neuropediatrics

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“…The low nanomolar concentrations of 3-MT, closely following the dynamics of extracellular DA levels, should be elevated by each administration of L-DOPA [61] . It is unknown what concentrations of 3-MT in the brain are produced by the chronic multi-year treatment of L-DOPA that is necessary to cause dyskinesias in PD patients, but a large increase in urine 3-MT levels have been reported in patients treated chronically with L-DOPA [62] , [63] . Thus, a potential contribution of elevated 3-MT levels to at least some specific manifestations of L-DOPA-induced dyskinesias and the role of TAAR1 in these processes deserve further detailed investigation.…”

Section: Discussionmentioning

confidence: 99%

The Dopamine Metabolite 3-Methoxytyramine Is a Neuromodulator

et al. 2010

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Dopamine (3-hydroxytyramine) is a well-known catecholamine neurotransmitter involved in multiple physiological functions including movement control. Here we report that the major extracellular metabolite of dopamine, 3-methoxytyramine (3-MT), can induce behavioral effects in a dopamine-independent manner and these effects are partially mediated by the trace amine associated receptor 1 (TAAR1). Unbiased in vivo screening of putative trace amine receptor ligands for potential effects on the movement control revealed that 3-MT infused in the brain is able to induce a complex set of abnormal involuntary movements in mice acutely depleted of dopamine. In normal mice, the central administration of 3-MT caused a temporary mild hyperactivity with a concomitant set of abnormal movements. Furthermore, 3-MT induced significant ERK and CREB phosphorylation in the mouse striatum, signaling events generally related to PKA-mediated cAMP accumulation. In mice lacking TAAR1, both behavioral and signaling effects of 3-MT were partially attenuated, consistent with the ability of 3-MT to activate TAAR1 receptors and cause cAMP accumulation as well as ERK and CREB phosphorylation in cellular assays. Thus, 3-MT is not just an inactive metabolite of DA, but a novel neuromodulator that in certain situations may be involved in movement control. Further characterization of the physiological functions mediated by 3-MT may advance understanding of the pathophysiology and pharmacology of brain disorders involving abnormal dopaminergic transmission, such as Parkinson's disease, dyskinesia and schizophrenia.

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“…The Figure 4 shows examples of the use of the synthesized internal standards for the quantitative mass spectrometric measurements of 3-0-methylated catecholamines in urine by a modification of our previously described method (9). Besides the positions of the labels, the main modifications Brown, S.S., Mitchell, F.L.…”

Section: Resultsmentioning

confidence: 99%

“…The then combined eluates were adjusted to pH 1 with a concentrated HC1 solution. Aliquots were evaporated to dryness at 4 0°C under a stream of nitrogen and derivatised with pentafluoropropionic anhydride as previously described ( 9 ) .…”

Section: ~~D _ R _ O _ L~s _~s _ -O _ F _ -T~~-~~~e _~~-~~~~~mentioning

confidence: 99%

Synthesis of CD₃‐labelled 3‐methoxytyramine, normetanephrine and metanephrine for use as internal standards in mass fragmentographic analyses

Muskiet

Pavel

Stob

et al. 1983

Labelled Comp Radiopharmac

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SUMMARYThe preparation of CD -labelled 3-methoxytyramine, normetanephrine and metanephrine from their parent catecholamines is described. The syntheses include N-maleylation, 0-methylation by dimethylsulfate-D6, removal of the protecting group by acid hydrolysis and partial purification of the reaction product. Examples of the use of the deuterium labelled 0-methylated catecholamine metabolites as internal standards for the ammonia chemical ionisation mass fragmentographic determination of their naturally occurring analogs in urine, are given. 3Key Words: CD -labelled-3-0-methylated catecholamine metabolites; mass 3 fragmentography .

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Determination of catecholamines and their 3-O-methylated metabolites in urine by mass fragmentography with use of deuterated internal standards.

Cited by 38 publications

References 0 publications

Kinetic Study of Catecholamine Metabolism in Hereditary Progressive Dystonia

Kinetic Study of Catecholamine Metabolism in Hereditary Progressive Dystonia

The Dopamine Metabolite 3-Methoxytyramine Is a Neuromodulator

Synthesis of CD₃‐labelled 3‐methoxytyramine, normetanephrine and metanephrine for use as internal standards in mass fragmentographic analyses

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Determination of catecholamines and their 3-O-methylated metabolites in urine by mass fragmentography with use of deuterated internal standards.

Cited by 38 publications

References 0 publications

Kinetic Study of Catecholamine Metabolism in Hereditary Progressive Dystonia

Kinetic Study of Catecholamine Metabolism in Hereditary Progressive Dystonia

The Dopamine Metabolite 3-Methoxytyramine Is a Neuromodulator

Synthesis of CD3‐labelled 3‐methoxytyramine, normetanephrine and metanephrine for use as internal standards in mass fragmentographic analyses

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Synthesis of CD₃‐labelled 3‐methoxytyramine, normetanephrine and metanephrine for use as internal standards in mass fragmentographic analyses