Metabolic Fate of 6,6,9-Trimethyl-9-azabicyclo [3,3,1]non-3β-yl α, α-Di (2-thienyl) glycolate Hydrochloride Monohydrate (PG-501)

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The isolation and identification of urinary metabolites of PG-501,a new antiparkinsonian agent, has been investigated in rats. PG-501 was extensively metabolized by rat since only less than 0.1% of the drug was recovered unchanged in the 24 hour urine. A part of PG-501 was first N-demethylated and then hydrolyzed, and almost all of the remainder was directly hydrolyzed to granatane base and α, α-di (2-thienyl) glycolic acid (DTGA). A part of granatane base was further metabolized by glucuronic acid conjugation. Most of DTGA was further metabolized by dethienylation, decarboxylation, glucuronic acid conjugation and mercapturic acid conjugation. The major metabolites of granatane base were 6,6,9-trimethyl-3-hydroxygranatane, 6,6-dimethyl-3-hydroxygranatane and their glucuronic acid conjugates whereas major metabolites of DTGA were glucuronic acid conjugate of DTGA, glucuronic acid conjugate of 2-thiophenecarboxylic acid, N-acetyl-S-[5-(2-thiophenecarbonyl)-2-thienyl]-L-cysteine, and 2-thiopheneglyoxylic acid. Studies of urinary metabolites of rats given N-^<14>CH_3-PG-501 showed that a part of formaldehyde produced by N-demethylation of the drug was excreted in urine as methionine, N-formylcysteine, N, N'-diformylcystine, formic acid and urea.
公益社団法人日本薬学会の論文
1972-08-25