Disease relevance of L-3-Methoxytyrosine

• Motor performance and dyskinesia correlated more closely with the time course of the appearance of levodopa in the ventricular cerebrospinal fluid than with the plasma levodopa concentration and did not correlate with plasma 3-O-methyldopa or cerebrospinal fluid 3-O-methyldopa or homovanillic acid [1].
• 3-O-methyldopa and motor fluctuations in Parkinson's disease [2].
• Demonstration of 3-methoxytyrosine in the urine of melanoma patients [3].
• With the aid of gas chromatography and mass spectrometry a metabolite of dopa, 3-methoxytyrosine, has been demonstrated in the urine of 2 patients with melanoma metastases, the amounts excreted being 4.0 mg and 8.5 mg/24 hours, respectively [3].
• Catechol-O-methyltransferase attenuates toxicity of levodopa in vitro by its metabolism to nontoxic 3-O-methyldopa [4].

High impact information on L-3-Methoxytyrosine

• To determine if 3-O-methyldopa (3OMD) significantly inhibits the transport of 6-[18F]fluorodopa (6-FD) into the brain at the concentration normally encountered during L-dopa administration, we performed 6-FD studies with positron emission tomography in cynomolgus monkeys in the presence and absence of 3OMD [5].
• 3-O-methyldopa blocks dopa metabolism in rat corpus striatum [6].
• Even when levodopa is co-administered with an inhibitor of AAAD such as benserazide or carbidopa, the bulk (90%) of levodopa is converted by COMT to the therapeutically inactive 3-O-methyldopa [7].
• The main finding was that entacapone does not alter the concentration-effect curve of levodopa, suggesting that entacapone acts at the level of peripheral pharmacokinetics of levodopa and that plasma levels of 3-O-methyldopa have a negligible role in the pharmacodynamics of levodopa [8].
• Improvement in dyskinesia was apparent by the second day of continuous levodopa, during which ratios of plasma dopa/3-O-methyldopa remained constant [9].

Chemical compound and disease context of L-3-Methoxytyrosine

• We determined concentrations of 3-O-methyldopa (3-OMD), L-3,4-dihydroxyphenylalanine (L-dopa), dopamine (DA) and other related substances in the cerebrospinal fluid in patients with Parkinson's disease (PD) 15 h after L-dopa/carbidopa medication, and compared patients with and without the wearing-off phenomenon [10].
• Pharmacokinetic behaviour of levodopa and 3-O-methyldopa after repeat administration of levodopa/carbidopa with and without entacapone in patients with Parkinson's disease [11].
• We studied the influence of dietary protein intake on the plasma level profile of levodopa, carbidopa, and 3-O-methyldopa and clinical efficacy in 12 patients with idiopathic Parkinson's disease after intake of one levodopa-carbidopa 200/50 controlled release tablet (Sinemet CR; LC-CR) [12].

Biological context of L-3-Methoxytyrosine

• In human volunteers, both entacapone and tolcapone dose-dependently inhibit the COMT activity in erythrocytes, improve the bioavailability and decrease the elimination of levodopa, and inhibit the formation of 3-O-methyldopa (3-OMD) [13].
• Estimates of C(max), t(max) and AUC of 3-O-methyldopa under non-fasting conditions were not significantly different from those under fasting conditions [14].
• Serum levels of DOPA and 3-O-methyldopa were linearly related in ultrafiltered serum water compared to perchloric acid-treated serum samples, suggesting little protein binding [15].
• This study aims to evaluate whether or not the kinetics of L-dopa, its main metabolites (3-O-methyldopa, 3-OMD, homovanilic acid, HVA and 3,4-dihydroxyphenylacetic acid, DOPAC) and carbidopa, vary according to the 24-hour scale in rats [16].

Anatomical context of L-3-Methoxytyrosine

• In the present study in vivo microdialysis sampling coupled to high-performance liquid chromatography with electrochemical detection, was used to study the pharmacokinetics of levodopa and 3-O-methyldopa in skeletal muscle in dog, after intravenous administration of levodopa [17].
• A possible defense mechanism is by means of metabolic shunting of levodopa excess to 3-O-methyldopa by COMT in peripheral and central nervous system tissues [4].
• Proceedings: Significance of 3-methoxytyrosine and its metabolites in urine of patients with sympathetic nervous system tumours [18].
• Since motor fluctuations in Parkinsonian patients might be, at least in part, explained by an antagonism between levodopa (LD) and its metabolite 3-O-methyldopa (3-OMD) at blood-brain-barrier (BBB), we decided to study LD and 3-OMD plasma and cerebrospinal fluid (CSF) levels in subjects undergoing lumbar puncture for diagnostic purposes [19].
• In neurochemical studies in rats, neither nitecapone (3 mg/kg) nor Ro 41-0960 (3 mg/kg) enhanced the levodopa/carbidopa (15/30 mg/kg)-induced dopamine levels in the hypothalamus and striatum, whereas 3-O-methyldopa (3-OMD) levels were suppressed [20].

Associations of L-3-Methoxytyrosine with other chemical compounds

• Concentrations of L-dopa, 3-methoxytyrosine, and 5-hydroxytryptophan were elevated in CSF, plasma, and urine [21].
• The activities of L-aromatic amino acid decarboxylase (dopa D), tyrosine hydroxylase, monoamine oxidase and catechol-O-methyl transferase were examined; in addition the tissue levels of dopa, 3-O-methyldopa, dopamine (DA) and homovanillic acid (HVA) were determined [22].
• In addition the identification of 3-O-methylDOPA, the extraneuronal metabolite of DOPA is not only the precursor of dopamine in the DRG but may be released from DRG cells [23].
• 3-Methoxytyramine could not be detected in brain and liver after treatment with L-3-methoxytyrosine [24].
• A concurrent increase in plasma 3-O-methyldopa (3-OMD) and a decrease in plasma 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), the three major metabolites of levodopa, suggests an inhibition of the enzyme dopa decarboxylase, probably by isoniazid [25].

Gene context of L-3-Methoxytyrosine

• They induce a dose-dependent inhibition of COMT activity in erythrocytes and a significant decrease in the plasma levels of 3-O-methyldopa, indicating their effectiveness as COMT inhibitors [26].
• Levodopa and dopamine are metabolized to 3-O-methyldopa and 3-methoxytyramine, respectively, by the enzyme catechol-O-methyltransferase (COMT) leading to the production of the demethylated cofactor S-adenosylhomo-cysteine (SAH) and subsequently homocysteine (HC) [27].

Analytical, diagnostic and therapeutic context of L-3-Methoxytyrosine

• To determine whether levodopa reduces the levels of S-adenosylmethionine in the human central nervous system, cerebrospinal fluid (CSF) concentrations of S-adenosylmethionine, methionine, 3-methoxytyrosine, levodopa and 5-methyltetrahydrofolate were measured in six children with dopamine deficiency before and after treatment [28].
• The present report describes a method using column liquid chromatography with electrochemical detection for assaying concentrations of 3-O-methyldopa in urine and plasma [29].
• In vivo pharmacokinetics of levodopa and 3-O-methyldopa in muscle. A microdialysis study [17].
• Blood levels of both L-dopa and 3-O-methyldopa (3-OMD) were assayed by HPLC in two different days, over an 8-hour period, before initiating cabergoline and at the end of the study [30].
• The agent 3-O-methyldopa is not toxic to cell cultures [4].

References