Biotransformation of moclobemide in humans

@article{Jauch1990BiotransformationOM,
  title={Biotransformation of moclobemide in humans},
  author={R Jauch and Eva Griesser and Gottfried Oesterhelt and Wolfgang Arnold and W. Melster and Walter H. Ziegler and Theodor W. Guentert},
  journal={Acta Psychiatrica Scandinavica},
  year={1990},
  volume={82}
}
The structure of the urinary metabolites formed after moclobemide administration in humans was elucidated, and the pattern compared with that in the plasma. The metabolic pathways of moclobemide were also compared with those of structurally related substances. After oral moclobemide administration, on average 95% of the dose was recovered in the urine within 4 days, with a mean of 92% being excreted during the first 12 h. The drug is extensively metabolized: less than 1 % of the dose was… Expand
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TLDR
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In vitro hepatic biotransformation of moclobemide (Ro 11-1163) in man and rat.
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All the in vitro models, but particularly hepatocytes, reflected the metabolism of moclobemide in vivo, Consequently, liver preparations can be used prospectively to screen the selectivity of related development compounds. Expand
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References

SHOWING 1-10 OF 11 REFERENCES
The fate of [14C]trithiozine in man.
1. Radioactivity of [14C]trithiozine (4-(3,4,5-trimethoxythiobenzoyl)tetrahydro-1,4-oxazine) was recovered quantitatively in the excreta within four days of a single dose (400 mg) given to four humanExpand
Biotransformation of Molsidomine (N-Ethoxycarbonyl-3-morpholinosydnonimine), a New Anti-anginal Agent, in Rats
Abstract1. After oral administration of [14C]N-ethoxycarbonyl-3-morpholinosydnon-imine (molsidomine) to rats, 85.0% of the ingested radioactivity was excreted in urine in 24 h. Metabolites found inExpand
Timolol metabolism in man and laboratory anamals.
The two major urinary metabolites of 14C-timolol in man, involving oxidation and hydrolytic cleavage of the morpholine ring, are also observed in both Sprague-Dawley rats and CRCD-1 mice. These areExpand
Metabolism of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (M73101), a new anti-inflammatory agent. II. Species differences of metabolism and excretion.
TLDR
For the effects of the dose administered on metabolism, dose-dependent variations of metabolism characteristic of guinea pigs were observed in biliary excretion and main metabolite was M-8 in low dose while M-9 in high dose but such phenomenon was not found in rats. Expand
The metabolism of [14C]N-ethoxycarbonyl-3-morpholinosydnonimine (molsidomine) in man.
TLDR
The main urinary radiolabelled metabolites appeared, from chromatographic evidence, to be similar to those previously identified in animals, namely N-morpholinosydnonimine, N-cyanomethylamino-N-(2'-hydroxyethyl)glycine and (N-cyAnomethylenamino-2-aminoethoxy)-acetic acid. Expand
Metabolites of 2-(3-trifluoromethylphenyl)tetrahydro-1,4-oxazine (CERM) 1841) in rats and dogs.
TLDR
In rats and dogs dosed with 14C-labelled 2-(3-trifluoromethylphenyl)tetrahydro-1,4-oxazine hydrochloride, the 14C was excreted in the urine and the faeces, andjugated metabolites accounted for the greater part of the urinary radioactivity in both species. Expand
The metabolism of phenyl o-(2-N-morpholinoethoxy)-phenyl ether hydrochloride in the rabbit and rat.
TLDR
The aromatic hydroxylation product, p-hydroxyphenyl o-(2-N-morpholinoethoxy)phenyl ether hydrochloride had vasopressor activity comparable with the parent compound, but with shorter duration of action. Expand
The metabolism of [ 14 C ] N - ethoxycarbonyl - 3 - morpholinosyd - nonimine ( molsidomine ) in man
  • Xenobiotica
  • 1987
WALK- ER RW, VANDENHEWEL WJA. Timolol metabolism in man and laboratory animals
  • in rats and dogs. Xenobiotica
  • 1987
The fate of [ 14 C ] trithiozine in man
  • Xenobiotica
  • 1982
...
1
2
...