3-Methoxy-4-hydroxyphenylacetic acid

Creosol (also called 2-methoxy-jb-cresol, 4-methylguaiacol, and 3-methoxy-4-hydroxytoluene) has been obtained by the fractionation of beach creosote tar,4 by the reduction of vanillin by electrolytic methods,6 6 by hydrogen and palladium on charcoal or barium sulfate,7 8 with hydrazine,9 and by amalgamated zinc and hydrochloric acid.3 10 11 It has also been prepared by methyl-ation of 4-methylcatechol with methyl iodide 12 13 or with methyl sulfate 14 and is reported to be formed by the distillation of the calcium salt of 3-methoxy-4-hydroxyphenylacetic acid.16... 

Disposition in the Body. Dopamine is a naturally occurring catecholamine and is considered to be the metabolic precursor of noradrenaline. It is inactivated after oral administration. It is excreted mainly as 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylacetic acid (homovanillic acid) noradrenaline and 3-methoxytyramine are also metabolites. Dopamine is a metabolite of levodopa. 

Disposition in the Body. Rapidly absorbed from the small bowel after oral administration and widely distributed in the tissues less than 1% of a dose reaches the brain bioavailability about 33%. Extensively metabolised mainly by decarboxylation to dopamine, which is further metabolised, and also by methylation to 3-0-methyldopa which accumulates in the central nervous system most of a dose is decarboxylated by the gastric mucosa before entering the systemic circulation the decarboxylase activity is inhibited by carbidopa and benserazide. Dopamine is further metabolised to noradrenaline, 3-methoxytyramine, and to the two major excretory metabolites, 3,4-dihydroxyphenyl-acetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylacetic acid (homovanillic acid, HVA). During prolonged therapy, the rate of levodopa metabolism appears to increase, possibly due to enzyme induction. About 70 to 80% of a dose is excreted in the urine in 24 hours. Of the material excreted in the urine, about 50% is DOPAC and HVA, 10% is dopamine, up to 30% is... 

Dopamine is also inactivated by monoamine oxidase to give 3,4-dLhydroxy-phenylacetic acid which is further metabolized by catechol 0-methyl-transferase to give 3-methoxy-4-hydroxyphenylacetic acid (homovanillic acid) . 

In the nigrostriatal system of PD patients, the activity of remaining TH increases following cell loss (Nagatsu, 1990). The elevated homovanillic acid (3-methoxy-4-hydroxyphenylacetic acid)/DA ratio in the striatum, which begins at a DA reduction of 50-60%, is proof of increased metabolism in the remaining neurons. 

The neurotoxic substance MPTP produces a clinical syndrome strikingly similar to idiopathic PD in humans (Langston et al., 1983), and induces nigrostriatal cell loss with concomitant decrease in DA and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid (3-methoxy-4-hydroxyphenylacetic acid), in monkeys (Burns et... 

The greater amount of dopamine that is formed in the brain after orally administered levodopa/carbidopa presumably provides symptomatic relief of parkinsonian symptoms, such as rigidity and bradykinesia. Parkinsonian patients not previously treated with levodopa usually are started on a combination therapy with Sinemet, which is available in a fixed ratio of 1 part carbidopa and 10 parts levodopa. Once formed from levodopa, metabolism of dopamine then proceeds relatively rapidly to the principal excretion products 3,4-dihydroxyphenylacetic acid and 3-methoxy-4-hydroxyphenylacetic acid (homovanillic acid) (Fig. 25.2). 

Correlations Between a Fluorimetric and Mass Fragmentographic Method for the Determination of 3-Methoxy-4-hydroxyphenylacetic Acid and Two Mass Fragmentographic Methods for the Determination of 3-Methoxy-4-hydroxyphenylethylene Glycol in Cerebrospinal Fluid J. Neurochem. 32(1) 191-194 (1979) ... 

A number of catecholamine metabolites have been demonstrated or found in increased amounts in the urine or in tumour tissue. The following metabolites occur in the urine 3,4 dihydroxyphenylacetic acid, 3-methoxytyramine, 3-methoxy-4-hydroxyphenylacetic acid (homo-vanillic acid), A-acetyldopamine, protocatechu-... 

A, adrenaline COMT, catechol-O-methyl transferase CSF, cerebrospinal fluid DA, 3,4-dihydroxyphenylethylamine (dopamine) Dopa, 3,4-dihydroxyphenylalanine 5HIAA, 5-hydroxyindoleacetic acid 5HT, 5-hydroxytryptamine (serotonin) 5HTP, 5-hydroxytryptophan HVA, 3-methoxy-4-hydroxyphenylacetic acid (homovanillic acid) MAO, monoamine oxidase MAOI, monoamine oxidase inhibitor MHPG,... 

On oxidation, homovanillic acid, HVA (4-hydroxy-3-methoxy-phenyl-acetic acid), is converted to a highly fluorescent, stable compound with an excitation wavelength of 315 nm and an emission wavelength of 425 nm. Oxidized HVA is produced in an amount proportional to that of GOase between 0.001 and 0.25 U/ml (Guil-bault, 1968). Guilbault (1976) showed that p-hydroxyphenylacetic acid has some advantages over HVA with respect to cost and fluorescence coefficient (fluorescence/concentration) and 0.01 U of enzyme could be assayed. 

For each type of assay, the label or tag involved is listed along with typical substrates, type of absorbance, and type of instrument required. RIA radioimmunoassay IRMA immunoradiometric assay CPM counts per minute ELISA enzyme linked immunosorbent assay EIA enzyme immunoassay TMB 5,5 tetramethylbenzidine HPA p hydroxyphenylacetic acid AMPPD 4 methoxy 4 (3 phosphatephenyl) spiro(l,2 dioxetane) 3,2 adamantane p NPP p nitrophenyl phosphate 4 MUP 4 methylumbelliferyl phosphate ONPG o nitrophenyl P galactopyranoside MUG 4 methylumbelliferyl P D galactopyrano side AMPGD 3 (4 methoxyspiro( 1,2 dioxetane 3,2 tricyclo(3.3.1.1(3,7))decan) 4 yl)phenylgalacto pyranoside ECL electrochemiluminescence. 

The kinetics of oxidation of substituted mandelic acids (a-hydroxyphenylacetic acid) in sulfate and mixed perchlorate/sulfate solutions are the subject of the four reports from Calvaruso et al. (1981a, b) and Arcoleo et al. (1977,1979). The oxidation reaction yields (substituted) benzaldehydes upon decarboxylation of mandelic acid. The oxidation of the p-nitro and p-methoxy derivatives in sulfuric acid proceeds without significant complex formation. The authors conclude that the reaction proceeds through two reactive Ce(IV) species,... 

When quercetin-3-rhamnoside was incubated anaerobically with human intestinal bacteria, quercetin, 3,4-hihydroxyphenylacetic acid, and 4-hydroxy-benzoic acid were produced as metabolites [106]. Analysis of urinary metabolites after orally administered mtin labeled with deuterium [(2, 5, 6 -2H]mtin led to the detection of 3-hydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylacetic... 

Obtained (by-product) by reaction of p-hydroxyphenylacetic acid with m-methoxy-phenol in ethylene dichloride in the presence of boron trifluoride at 80° for 2 h under an argon atmosphere (2%) [5439]. 

The methoxy substituent (14c) showed a much cleaner behavior, yielding only two products from the chromophore,p-methoxyacetophenone and the rearrangement product p-methoxyphenylacetic acid. The p-hydroxyphenacyl phosphate (33) gave the rearranged p-hydroxyphenylacetic acid when photolyzed in mixed aqueous organic solvents (Eq. (69.12)) in fact, of all of the groups examined, only p-hydroxy and p-methoxy produced any rearranged phenylacetic acids. 

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