3.4- Dihydroxyphenyl acetic acid

The main metabolic routes of dopamine and noradrenaline in the brain. COMT, Catechol O-methyltransferase MAO, monoamino oxidase DDC, dopa decarboxylase DBH, dopamine (3-hydroxylase 3-OMD, 3-methoxytyrosine Dopac, dihydroxyphenyl acetic acid. 

Table 1. Significant increase (P<0.05, t-test) in dihydroxyphenyl acetic acid (DOPAC) and 5-hydroxyindol acetic acid (5-HIAA) in the mouse hypothalamus following treatment of mice with Agaricus muscarius 12 through the oral route. No significant change in the level of dopamine (DA) and serotonin (5 HT) was observed. Data from Sc Cult 56 134-135 (1990) reproduced with author s permission.

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... 

The beneficid effects of olive oil phenols have been shown in a number of studies in vitro. Investigations in vivo are rare due to the lack of commercially available compounds. Recently a group in Japan has published the first study on the determination of hydroxytyrosol in plasma after oral administration to rats by GC-MS quantitative method [98]. Hydroxytyrosol of 98% purity (as estimated from NMR) was synthetized in high yield (90%) and in gram-scale from 3,4-dihydroxyphenyl acetic acid. 

M (decreased motor activity increased concentrations of 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenyl- acetic acid, dopamine in the hypothalamus)... 

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. 

Dopamine concentrations are reduced and dopamine metabolites dihydroxyphenyl-acetic acid (DOPAC), homovanillic acid (HVA) are increased by ibogaine under certain experimental conditions, for example, when measurements are taken shortly (within 2 h) after ibogaine administration or when relatively high concentrations (s 100 /uM) are used (69,71,76,81,169-173). Reductions in extracellular dopamine concentrations were also observed after administration of a number of ibogaine derivatives, including O-desmethylibogaine (89) and 18-methoxycoronari-dine (97). 

Carbon and ceramic electrodes have been used for quantitative and qualitative recordings of the neurotransmitters dopamine (DA), 5-hydroxytryptamine (5-HT), and their metabolites 3,4-dihydroxyphenyl-acetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA), and L-glutamate. Nitric oxide can also be recorded. In this case the carbon surface of the electrode is covered with a p-type semiconducting polymeric porphyrin that acts as a catalyst for the oxidation of nitric oxide. Nitric oxide is responsible for the activity of the endothelium-derived relaxing factor associated with hypertension, diabetes, ischemia, and arteriosclerosis. 

E. Nissinen, and J. Taskinen, Simultaneous determination of carbidopa, levodopa and 3,4-dihydroxyphenyl-acetic acid using high-performance liquid chromatography with electrochemical detection, J. Chromatogr., 1982, 231, 459-462. 

Homogentisic Acid (2 5-Dihydroxyphenyl-acetic acid, 2 5-dihydroxy-a-toluic acid)... 

Helgeson, E., and Davis, J. M. Simultaneous Determination by GC-MS-SIM of 0-, m-, p-Hydroxyphenyl-acetic Acid, 3,4-Dihydroxyphenyl-acetic Acid and Homovanillic Acid in Biological Samples Using a Common Selected Ion J. Chromatogr. Sci. 16(6) 263-267 (1978) CA 89 175847w... 

N. D. = not determined in cited studies, FLD = fluorescent detection, ECD = electrochemical detection, PFET = photoluminescence following electron transfer, DOPAC = 3,4-dihydroxyphenyl acetic acid, 5-HIAA = 5-hydroxyindoleacetic acid, HVA = homovanillic acid, 3-MT = 3-methoxytyramine, 2-AG = 2-arachidonyl glycerol, AEA = amandamide, CGRP = calcitonin—gene-related peptide. 

Figure 3. Structural models of adsorbed molecules at Pt(lOO) and Pt(lll) surfaces. (A) L-dopa (LD) (B) L-Tyrosine (TYR) (C) L-cysteine (CYS) (D) L-phenylalanine (PHE) (E) L-alanine (ALA) (F) dopamine (DA) (G) catechol (CT) (H) 3,4-dihydroxyphenyl-acetic acid (DOPAC).

Benzo-12-crown-4, B-00052 (3,4-Dihydroxyphenyl)acetic acid Di-Me ether, Et ester, in D-00687... 

Pyrenesulfonic acid, P-00309 Sorbitan tristearate, in A-00367 (3,4-Dihydroxyphenyl)acetic acid,... 

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