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T. Niwaguchi

5 papers in the library · 10 citations · publishing 1974-1980

Papers

Enzymic formation of dehydrogenated and hydroxylated metabolites from lysergic acid diethylamide by rat liver microsomes

Xenobiotica January 1, 1980 T. Inoue, T. Niwaguchi, T. Murata 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.

Effects of inducers and/or inhibitors on metabolism of lysergic acid diethylamide in rat liver microsomes

Xenobiotica January 1, 1980 T. Inoue, T. Niwaguchi, Toshiro Murata 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.

ChemInform Abstract: STUDIES ON LYSERGIC ACID DIETHYLAMIDE AND RELATED COMPOUNDS PART 3, INPROVEMENT OF AMIDATION OF LYSERGIC ACID

Chemischer Informationsdienst August 20, 1974 Y. Nakahara, T. Niwaguchi

Amidation of lysergic acid (I) using triphenyl phosphite/imidazole/phosphoric acid tris-(dimethylamide) or phosphoric acid tris-(dimethylamide)/tosyl chloride yields compounds (II) and (III). With the latter reagent, compounds (II) are obtained in 68-75% yield and compounds (III) in up to 3-8% yield.