Biotransformation of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid to harmalan, tetrahydroharman and harman in rats.
1-Methyl-1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid (1-carboxytetrahydroharman, 1-CTHH) has been detected in the brain of rats following intracerebroventricular injection of tryptamine and pyruvic acid. We now report the metabolism of this compound. Following intraperitoneal injection of 1-CTHH into rats, harmalan was found to be the major metabolite besides tetrahydroharman (THH) and harman. A high concentration of THH was measured in the lung while most of harman was found in the urine. Harmalan and THH could be detected in the brain in low concentrations. The products were separated following extraction from tissues by high-performance liquid chromatography (HPLC) on a reversed phase C18-DB column. The identity of the metabolites was confirmed by mass spectrometry (MS) analysis. The results demonstrate the role of 1-CTHH as a precursor of the biologically active compounds harmalan, THH and harman.
Institut für Neuropsychopharmakologie, Freie Universität Berlin, F.R.G.
R
R
Susilo
H
H
Damm
H
H
Rommelspacher
G
G
Höfle
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002243:Carbolines / Q000008:administration & dosage / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006246:Harmaline / Q000031:analogs & derivatives / Q000378:metabolism; D006247:Harmine / Q000031:analogs & derivatives / Q000652:urine; D007274:Injections, Intraperitoneal; D051381:Rats; D011919:Rats, Inbred Strains; D014781:Viscera / Q000378:metabolism*
D002243:Carbolines; C023426:tetrahydroharmane; D006247:Harmine; C045323:harmalan; C052025:1,2,3,4-tetrahydro-1-methyl-beta-carboline-1-carboxylic acid; C005010:harman; D006246:Harmaline