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Titolo:
Metabolites of [C-14]-5-(2-ethyl-2H-tetrazol-5-yl)-1-methyl-1,2,3,6-tetrahydropyridine in mice, rats, dogs, and humans
Autore:
Christensen, EB; Andersen, JB; Pedersen, H; Jensen, KG; Dalgaard, L;
Indirizzi:
H Lundbeck AS, Dept Drug Metab, Res & Dev, DK-2500 Copenhagen, Denmark H Lundbeck AS Copenhagen Denmark DK-2500 ev, DK-2500 Copenhagen, Denmark
Titolo Testata:
DRUG METABOLISM AND DISPOSITION
fascicolo: 11, volume: 27, anno: 1999,
pagine: 1341 - 1349
SICI:
0090-9556(199911)27:11<1341:MO[>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
ALDEHYDE OXIDASE; ARECOLINE; LIVER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
12
Recensione:
Indirizzi per estratti:
Indirizzo: Christensen, EB H Lundbeck AS, Dept Drug Metab, Res & Dev, Ottiliavej 9, DK-2500 Copenhagen, Denmark H Lundbeck AS Ottiliavej 9 Copenhagen Denmark DK-2500 ark
Citazione:
E.B. Christensen et al., "Metabolites of [C-14]-5-(2-ethyl-2H-tetrazol-5-yl)-1-methyl-1,2,3,6-tetrahydropyridine in mice, rats, dogs, and humans", DRUG META D, 27(11), 1999, pp. 1341-1349

Abstract

The M1 muscarine agonist, 5-(2-ethyl-2H-tetrazol-5-yl)-1-methyl-1,2,3,6-tetrahydropyridine (Lu 25-109), is extensively metabolized in mice, rats, dogs, and humans. The metabolite profile after an oral dose of [C-14]Lu25-109 was determined in plasma and in urine. Lu 25-109 was metabolized by N-demethylation (Lu 25-077), N-oxidation (Lu 32-181), and N-deethylation (Lu 31-126). In addition, combined N-demethylation and N-deethylation (Lu 31-190), and formation of a pyridine derivative took place (Lu 31-102). Lu 25-109 wasalso oxidized to pyridinium (Lu 29-297), 3-hydroxy-pyridinium (Lu 35-080),N-deethyl-2-pyridone (Lu 35-026), and a glucuronide of a 4,6-dihydroxy-pyridinium ("m/z 398") compounds. A glucuronide of a dihydroxylated dihydro-pyridine compound ("m/z 400") was isolated from human urine, but not fully identified. In vitro studies were undertaken to elucidate the order of formation of the metabolites. In human plasma, the concentrations of Lu 25-109 and the pharmacologically active N-demethyl metabolite (Lu 25-077) were smallcompared with the N-oxide (Lu 32-181) and the N-deethyl-2-pyridone (Lu 35-026) at the first sample time (0.75 h). The N-deethyl metabolite (Lu 31-126) was the major component in human plasma between 3 and 10 h postdose. The major human metabolites in urine (Lu 32-181, Lu 35-026, and Lu 31-126) and the minor metabolites (Lu 25-077, Lu 35-080, Lu 31-190, and Lu 29-297) wereall present in urine from rats, dogs, and mice, whereas m/z 398 was present in only mice and humans, and Lu 31-102 in only rats. The minor human metabolite m/z 400 was not detected in mice, rats, or dogs.

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Documento generato il 03/07/20 alle ore 01:46:42