ABSORPTION, METABOLISM AND DISTRIBUTION OF [14C]‐O‐METHYLDOPA AND [14C]‐<scp>l</scp>‐DOPA AFTER ORAL ADMINISTRATION TO RATS

Rivera‐Calimlim, Leonor

doi:10.1111/j.1476-5381.1974.tb08570.x

Cited by 16 publications

(6 citation statements)

References 9 publications

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“…Paired compar isons between regions did demonstrate some signif icant differences between regional values (e.g., be tween basal ganglia and occipitoparietal cortex) although the magnitude of these differences was not large. The variability across animals of the esti mates was moderate, ranging between 10 and 20% for KJ in all regions and 5 to 15% for Ve' DISCUSSION Overall, our findings are consistent with those previously obtained in other species (Rivera Calimlin, 1974;Wade and Katzman, 1975;Rose et J Cereb Blood Flow Metab, Vol. ll, No.5, 1991 aI., 1988).…”

Section: Resultssupporting

confidence: 83%

“…This suggests that there is no significant trapping of eSF]3-0M-DOPA in the striatum or other brain ar eas. These findings make it very unlikely that eSF]3-0M-DOPA undergoes further metabolism in the brain, in particular to eSF]DOPA, contrary to what earlier reports suggested (Rivera-Calimlin, 1974).…”

Section: Resultscontrasting

confidence: 55%

“…The metabolite data suggest that [' s F]3-0M DOPA is not converted into [, s F]DOPA at any point during the 3 h following its administration. How ever, we cannot rule out that small quantities of [l s F]DOPA are produced as earlier studies sug gested (Rivera-Calimlin, 1974). In such instance, the quantities of [, s F]DOPA would have had to have been extremely small to have eluded our abil ity to detect its selective striatal accumulation and its presence in the plasma.…”

Section: Resultsmentioning

confidence: 99%

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Distribution and Kinetics of 3-O-Methyl-6-[¹⁸F]fluoro-L-DOPA in the Rhesus Monkey Brain

Doudet¹,

McLellan²,

Carson³

et al. 1991

J Cereb Blood Flow Metab

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Summary: Most attempts to model accurately [18FI_ DOPA imaging of the dopamine system are based on the assumptions that its main peripheral metabolite, 3-crosses the blood-brain barrier but is present as a homog enous distribution throughout the brain, in part because it is not converted into e8F]DOPA in significant quantities, These assumptions were based mainly on data in rodents. Little information is available in the primate. To verify the accuracy of the above assumptions, we administered 1 8F-labeled 3-0M-DOPA to normal rhesus monkeys and animals with lesions of the DA nigrostriatal system. NoIn recent years, positron emission tomography (PET) has become an increasingly used tool to dem onstrate normal and abnormal brain functions in multiple neurological and neuropsychiatric disor ders. Apart from eSF]deoxyglucose and blood flow agents, considerable interest has been given to the investigation of tracers selective for the dopaminer gic (DA) system. Numerous clinical and pharmaco logical studies have shown that abnormalities in this

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Section: Resultssupporting

confidence: 83%

Section: Resultscontrasting

confidence: 55%

Section: Resultsmentioning

confidence: 99%

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Distribution and Kinetics of 3-O-Methyl-6-[¹⁸F]fluoro-L-DOPA in the Rhesus Monkey Brain

Doudet¹,

McLellan²,

Carson³

et al. 1991

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

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“…This enzyme, which is highly expressed in the liver and GI tract (Uhlén et al, 2015), methylates dopamine to the aryl methyl ether 3-methoxytyramine (3MT) (Figure 1). There are several examples of gut bacteria O-demethylating aryl methyl ethers (Bess et al, 2019;Clavel, Borrmann, et al, 2006;Misoph et al, 1996;Sharak Genthner & Bryant, 1987) demethylation of 3-O-methyldopa only occurred once this compound was excreted in bile to the GI tract; no demethylation occurred in rats with fistula that prevented biliary excretion (Rivera-Calimlim, 1974). These findings indicate that 3-O-methyldopa, which is structurally analogous to 3MT, is O-demethylated in vivo, but only upon entering the GI tract.…”

Section: Introductionmentioning

confidence: 92%

Alternative pathway for dopamine production by acetogenic gut bacteria that O-Demethylate 3-Methoxytyramine, a metabolite of catechol O-Methyltransferase

Rich

Jackson

Ora

et al. 2022

Journal of Applied Microbiology

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Aims:The gut microbiota modulates dopamine levels in vivo, but the bacteria and biochemical processes responsible remain incompletely characterized. A potential precursor of bacterial dopamine production is 3-methoxytyramine (3MT); 3MT is produced when dopamine is O-methylated by host catechol O-methyltransferase (COMT), thereby attenuating dopamine levels. This study aimed to identify whether gut bacteria are capable of reverting 3MT to dopamine. Methods and Results: Human faecal bacterial communities O-demethylated 3MT and yielded dopamine. Gut bacteria that mediate this transformation were identified as acetogens Eubacterium limosum and Blautia producta. Upon exposing these acetogens to propyl iodide, a known inhibitor of cobalamin-dependent O-demethylases, 3MT O-demethylation was inhibited. Culturing E. limosum and B. producta with 3MT afforded increased acetate levels as compared with vehicle controls. Conclusions: Gut bacterial acetogens E. limosum and B. producta synthesized dopamine from 3MT. This O-demethylation of 3MT was likely performed by cobalamindependent O-demethylases implicated in reductive acetogenesis. Significance and Impact of the Study: This is the first report that gut bacteria can synthesize dopamine by O-demethylation of 3MT. Owing to 3MT being the product of host COMT attenuating dopamine levels, gut bacteria that reverse this transformation-converting 3MT to dopamine-may act as a counterbalance for dopamine regulation by COMT.

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“…14, No.4, 1994 1991). A possible explanation for this finding is , that small quantities of OMFD are demethylated to F-dopa in the striatum (Revera-Calimlin, 1974).…”

Section: Time (Minutes)mentioning

confidence: 99%

The Distribution and Kinetics of [¹⁸F]6-Fluoro-3-O-Methyl-l-Dopa in the Human Brain

Wahl

Chirakal

Firnau

et al. 1994

J Cereb Blood Flow Metab

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Summary: The analysis of positron tomographic studies of 3,4-dihydroxyphenylethylamine (dopamine) metabo lism in which e8F]6-fluoro-L-3,4-dihydroxyphenylalanine (F-dopa) is used as a tracer is confounded by the presence of [18Fj6-fluoro-3-0-methyl-L-3,4-dihydroxyphenylala nine (OMFD). This labeled molecule, formed by the ac tion of peripheral cathechol-O-methyltransferase on F-dopa, crosses the blood-brain barrier and contributes to the radioactivity measured by the tomograph. Correc tions for this radioactivity in the brain have been pro posed. They rely upon the assumption that regional vari ations in the handling of this molecule by the brain are negligible. Although this assumption is pivotal for the proper quantification of dopamine metabolism using F-dopa, the distribution and kinetics of OMFD have never been studied in humans. We present results in hu mans that show that there is little selective regional 18F accumulation in the brain, that the distribution volume of Positron tomography used with a labeled precur sor of 3,4-dihydroxyphenylethylamine (dopamine) offers the best approach to the investigation of pre synaptic dopamine metabolism in living humans. The most commonly used tracer is an analogue of L-3,4-dihydroxyphenylalanine (L-dopa) labeled with fluorine-I 8: [ l sF16-fluoro-L-dopa (F -dopa). How ever, the analysis of the data has been confounded by the presence of other labeled species formed in the body, which cross the blood-brain barrier. Like L-dopa, F-dopa acts as a substrate for catechol-OReceived June 9, 1993; final revision received December 9, 1993; accepted January 12, 1994. 664OMFD is close to unity, and that a single, reversible com partment is adequate to model the measured time course of radioactivity after an OMFD injection. Analysis of plasma samples for labeled metabolites showed that more than 95% of the radioactivity was associated with OMFD at all times. Our results for OMFD kinetics are in accord with published results obtained in nonhuman primates and for the bidirectional transport of large neutral amino acids across the blood-brain barrier measured using a synthetic amino acid. However, our results also indicate that there are small but significant differences in OMFD kinetics in different parts of the brain that may prevent inferences about the handling of OMFD in one part of the brain from being extended to other parts of the brain. Key Words: Compartmental analysis-Dopamine metabo lism-6-Fluoro-3-0-methyl-L-dopa-6-Fluoro-L-dopa Graphical analysis-Positron tomography-Striatum. methyltransferase (COMT), forming eSF16-fluoro-3-0-methyl-L-dopa (OMFD). OMFD, formed in the peripheral organs and the red blood cells, is able to cross the blood-brain barrier and contributes to the radioactivity measured by the tomograph. Correc tions for this radioactivity in dopaminergic regions of the brain have been proposed (Martin et aI. , 1989; Huang et aI. , 1991; Gjedde et aI. , 1991; Chan et aI., 1992). These corrections usually rely upon one or more of the following assumptions: t...

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ABSORPTION, METABOLISM AND DISTRIBUTION OF [¹⁴C]‐O‐METHYLDOPA AND [¹⁴C]‐l‐DOPA AFTER ORAL ADMINISTRATION TO RATS

Abstract: 1The absorption, tissue distribution, and metabolism of [14C] -0-methyldopa were compared with those of [14C]-L-DOPA after oral administration to ratf.

Cited by 16 publications

References 9 publications

Distribution and Kinetics of 3-O-Methyl-6-[¹⁸F]fluoro-L-DOPA in the Rhesus Monkey Brain

Distribution and Kinetics of 3-O-Methyl-6-[¹⁸F]fluoro-L-DOPA in the Rhesus Monkey Brain

Alternative pathway for dopamine production by acetogenic gut bacteria that O-Demethylate 3-Methoxytyramine, a metabolite of catechol O-Methyltransferase

The Distribution and Kinetics of [¹⁸F]6-Fluoro-3-O-Methyl-l-Dopa in the Human Brain

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ABSORPTION, METABOLISM AND DISTRIBUTION OF [14C]‐O‐METHYLDOPA AND [14C]‐l‐DOPA AFTER ORAL ADMINISTRATION TO RATS

Abstract: 1The absorption, tissue distribution, and metabolism of [14C] -0-methyldopa were compared with those of [14C]-L-DOPA after oral administration to ratf.

Cited by 16 publications

References 9 publications

Distribution and Kinetics of 3-O-Methyl-6-[18F]fluoro-L-DOPA in the Rhesus Monkey Brain

Distribution and Kinetics of 3-O-Methyl-6-[18F]fluoro-L-DOPA in the Rhesus Monkey Brain

Alternative pathway for dopamine production by acetogenic gut bacteria that O-Demethylate 3-Methoxytyramine, a metabolite of catechol O-Methyltransferase

The Distribution and Kinetics of [18F]6-Fluoro-3-O-Methyl-l-Dopa in the Human Brain

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ABSORPTION, METABOLISM AND DISTRIBUTION OF [¹⁴C]‐O‐METHYLDOPA AND [¹⁴C]‐l‐DOPA AFTER ORAL ADMINISTRATION TO RATS

Distribution and Kinetics of 3-O-Methyl-6-[¹⁸F]fluoro-L-DOPA in the Rhesus Monkey Brain

Distribution and Kinetics of 3-O-Methyl-6-[¹⁸F]fluoro-L-DOPA in the Rhesus Monkey Brain

The Distribution and Kinetics of [¹⁸F]6-Fluoro-3-O-Methyl-l-Dopa in the Human Brain