Dopamine/norepinephrine ratio

The relative excretion of catecholamines and their metabolites may also point to an unfavorable outcome in neuroblastomas. Immature metabolic patterns have been observed in neuroblastoma tumor tissue, based on excretion of dopamine or HVA relative to norepinephrine or VMA. A high ratio of HVA/VMA, dopamine/VMA, or dopamine/ norepinephrine indicates a relative deficiency in beta hydroxylation with a reduction in tumor cell conversion of dopamine to norepinephrine. The immature metabolic pattern has been associated with aggressive tumor behavior and other unfavorable prognostic factors," but the clinical application of metabolic patterns has not been established. 

Of the clinically tested new antipsychotics, ziprasidone has the highest 5-HT2A/D2 receptor-affinity ratio. Ziprasidone is an antagonist at the a -adrenoreceptor, but its affinity is half that of its D 2 affinity. In addition, compared with its affinity for D 2 and 5-HT2A receptors, ziprasidone has a relatively low affinity for histamine receptors (pKJ = 7.33). In vitro, ziprasidone is a moderately potent inhibitor of neuronal reuptake of norepinephrine, serotonin, and, to a lesser extent, dopamine. This property is shared with some antidepressants, and contrasts with risperidone, which is inactive at all three monoamine uptake sites. 

Spin-casting techniques have also been used to prepare imprinted thin films. Makote and Collinson recently prepared metal oxide thin films imprinted with recognition sites for dopamine [18], The dopamine template was loaded at 4 mole % in a sol with a 10 1 ratio of tetramethoxysilane and phenyltrimethoxysilane. The prepared film had a thickness of ca. 450 nm. CV analysis found that 90% of the templates could be removed by washing the films with pH 7 phosphate buffer. The opened receptor sites offered selective binding for related molecules containing catechol amines, such as dopamine, epinephrine and norepinephrine, as determined by CV. The use of phenyltrimethoxysilane turns out to be an essential ingredient for the gel matrix and is believed to provide some complementary affinity for the catechol amines via hydrophobic and/or 7i-stacking interactions. 

The major clinical feature of patients with deficiency of dopamine p-hydroxylase is orthostatic hypotension caused by reduced synthesis and release of norepinephrine by sympathetic nerves. The deficiency is characterized neuro-chemically by decreased levels of norepinephruie and norepinephrine metabolites and increased levels of dopamine and dopamine metabolites. Diagnosis is best achieved from an increased ratio of plasma dopamine to norepinephrine. Copper deficiency in Menkes disease is due to defects in the gene coding for a copper-transporting adenosine triphosphatase. Because dopamine p-hydroxylase is a copper-dependent enzyme, the deficiency is associated with decreased activity of the enzyme and reduced production of norepinephrine from dopamine. Prompt diagnosis at childbirth is essential for copper-replacement therapy, and... 

Since L-tyrosine is the main precursor of melanins and a substrate of tyrosinase, the L-DOPA/L-tyrosine ratio could more accurately reflect tyrosinase activity than l-DOPA alone. In 1997, we developed two reversed-phase HPLC techniques, one with electrochemical detection to measure simultaneously l-DOPA, norepinephrine (NE), epinephrine (E), dopamine (DA), and DOPAC (3,4-dihydroxyphenyl acetic acid) (all compounds easily oxidizable between +0.15 and +0.50 V), and one with fluorimetric detection to measure L-tyrosine (and phenylalanine) on the same blood sample. 

Figure 4.2 Variation of retention time of l-DOPA as a function of pH of the mobile phase. As the pH increases, the retention time of l-DOPA decreases. NE, norepinephrine E, epinephrine DA, dopamine DHBA, internal standard. Reprinted from Journal of Chromatography B, 696, Letellier S, Gamier JP, Spy J, Bousquet B. Determination of the L-DOPA/L-tyrosine ratio in human plasma by high-performance liquid chromatography. Usefulness as a marker in metastatic malignant melanoma, pages 9-17, Copyright 1997, with permission from Elsevier...

It should be noted, that the Lacc-GDH recycling electrode does not distinguish between epinephrine, norepinephrine or dopamine. Nevertheless, the selectivity is sufficient for discriminating the catecholamine signal from other components of the stimulating buffer without any purification or separation step. If the ratio between epinephrine and norepinephrine shall be determined, on the basis of the bioelectrocatalytic substrate regeneration by GDH immobilized on a carbon electrode (15) norepinephrine can be detected 40 times more sensitive than epinephrine while 1 4 selectivity is observed for the Lacc-GDH electrode. The conventional HPLC procedure for determination of catecholamines requires complex and expensive devices since the electrochemical detector has only low selectivity. 

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