Xenobiotica
January 1, 1980
Robert Parker, P. C. Hirom, P. Millburn
46 citations
In female Wistar albino rats, biliary elimination of phenolphthalein, morphine, LSD, and diphenylacetic acid occurred predominantly as glucuronides, with 90%, 45%, 75%, and 57% of injected doses eliminated in bile within three hours. Infusing this bile into the duodena of other rats showed enterohepatic circulation: 85%, 41%, 28%, and 66% of the infused conjugates were reabsorbed and re-excreted over 24 hours. Suppressing intestinal bacteria with antibiotics reduced recirculation to 22%, 8.6%, and 21% for phenolphthalein, morphine, and diphenylacetic acid glucuronides, but did not affect absorption of free aglycones. This demonstrates that bacterial beta-glucuronidase hydrolysis of glucuronides is essential for enterohepatic circulation. Intestinal absorption of released aglycones correlated with their lipid-solubility, measured by octan-1-ol:phosphate buffer partition ratios.
Xenobiotica
November 3, 2008
Tatsuyuki Kanamori, Kenji Kuwayama, Kenji Tsujikawa et al.
11 citations
Alpha-methyltryptamine (AMT), a psychoactive tryptamine analogue, is metabolized in rats into at least four distinct compounds. After oral administration of 10 mg/kg to male Wistar rats, urine collected over 24 hours was enzymatically hydrolyzed, extracted, and analyzed by gas chromatography/mass spectrometry. The detected metabolites were 2-oxo-AMT, 6-hydroxy-AMT, 7-hydroxy-AMT, and 1'-hydroxy-AMT. These findings identify specific metabolic pathways for AMT, which may inform understanding of its pharmacological effects and duration of action.
Xenobiotica
January 1, 1980
7 citations
Rat liver microsomes metabolize LSD into several products. Two previously reported metabolites, lysergic acid ethylamide and nor-LSD, were found alongside two newly identified ones: lysergic acid ethylvinylamide, formed by dehydrogenation of the side chain, and 13-hydroxy-LSD, a phenol. Pretreatment of rats with phenobarbitone sodium induced formation of lysergic acid ethylamide, lysergic acid ethylvinylamide, and nor-LSD, while 3-methylcholanthrene induced lysergic acid ethylamide, lysergic acid ethylvinylamide, and 13-hydroxy-LSD. Nor-LSD formation was induced only by phenobarbitone, and 13-hydroxy-LSD only by methylcholanthrene.
Xenobiotica
January 1, 1980
3 citations
LSD metabolism in rat liver microsomes involves at least three separate enzyme systems. In untreated rats, the inhibitor SKF 525-A most potently blocked hydroxylation at the 13-position, moderately blocked N-demethylation at the 6-position, and least affected side-chain metabolism at the 8-position. A carbon monoxide/oxygen atmosphere (80% CO, 20% O2) caused maximum inhibition of N-demethylation, moderate inhibition of 13-hydroxylation, and minimum inhibition of side-chain metabolism. In microsomes from rats pretreated with 3-methylcholanthrene, 13-hydroxylation was not inhibited by CO but still required NADPH and oxygen, suggesting catalysis by an unusual cytochrome P-448 enzyme system.