Rapid hydroxylation of methtryptoline (1-methyltetrahydro-beta-carboline) in rat: identification of metabolites by chiral gas chromatography-mass spectrometry.
Racemic methtryptoline (1-methyltetrahydro-beta-carboline) and 5-hydroxymethtryptoline-9-carboxylic acid (6-hydroxy-1-methyltetrahydro-beta-carboline-1-carboxylic acid) were administered intraperitoneally to rats and the components of their urine was subsequently investigated by chiral gas chromatography-mass spectrometry. Methtryptoline rapidly became hydroxylated in the 5- and 6-position and excreted in urine. There was about a ninefold predominance of the S(-) enantiomer over the other in the 5-hydroxylated species, while the 6-hydroxylation produced a small excess of the R(+) enantiomer. About 75% of the injected dose of methtryptoline was recovered in the urine as 5- and 6-hydroxylated compounds during the first 24 h period, demonstrating that hydroxylation represents the major metabolic pathway. Treatment with 6-hydroxymethtryptoline-9-carboxylic acid led to a fivefold increase in the urinary excretion of 5-hydroxymethtryptoline during the first 24 h period with a predominance of the S(-)-enantiomer, indicating a much smaller conversion rate than from methtryptoline. It was concluded that hydroxylation of methtryptoline is a likely pathway for the natural formation of 5-hydroxymethtryptoline.
D000818:Animals; D002243:Carbolines / Q000378:metabolism* / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry; D006900:Hydroxylation; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D002243:Carbolines; C009777:2-methyltryptoline; C035602:6-hydroxy-1-methyltryptoline