Summary
Racemic methtryptoline (1-methyltetrahydro-β-carboline) and 5-hydroxymethtryptoline-9-carboxylic acid (6-hydroxy-1-methyltetrahydro-β-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.
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References
Agurell S, Holmstedt B, Lindgren J-E (1969) Metabolism of 5-methoxy-N,N-dimethyl-tryptamine-14C in the rat. Biochem Pharmacol 18:2771–2781
Airaksinen MM, Kari I (1981) β-Carbolines, psychoactive compounds in the mammalian body. Med Biol 59:21–34
Akibori S, Saito J (1930) Synthese von Harman and Harmin. Ber 63:2245–2248
Akimoto H, Okamura K, Yui M, Shioiri T, Kuramoto M, Kikugawa Y, Yamada S (1974) A new approach to the biogenetictype, asymmetric synthesis of indole and isoquinoline alkaloids by 1,3-transfer of asymmetry. Chem Pharmacol Bull 22:2614–2623
Allen JRF, Beck O, Borg S, Skröder R (1980) Analysis of 1-methyl-1,2,3,4-tetrahydro-β-carboline in human urine and cerebrospinal fluid by gas chromatography-mass spectrometry. Eur J Mass Spectrom 1:171–177
Allen JRF, Holmstedt BR (1980) The simple β-carboline alkaloids. Phytochemistry 19:1573–1582
Ayer WA, Browne LM (1970) Alkaloids of Shepherdia argentea and Shepherdia canadensis. Can J Chem 48:1980–1984
Beck O, Lundman A (1983), Occurrence of 6-hydroxy-1-methyl-1,2,3,4-tetrahydro-β-carboline in tissues and body fluids of rat. Biochem Pharmacol 32:1507–1510
Beck O, Faull KF (1985) Concentrations of the enantiomers of 5-hydroxymethtryptoline in mammalian urine: implications for in vivo biosynthesis. Biochem Pharmacol (in press)
Beck O, Bosin TR, Lundman A, Borg S (1982) Identification and measurement of 6-hydroxy-1-methyl-1,2,3,4-tetrahydro-β-carboline by gas chromatography-mass spectrometry. Biochem Pharmacol 31:2517–2521
Beck O, Faull KF, Barchas JD, Johnson JV, Yost RA (1985) Chiral analysis of urinary 5-hydroxymethtryptoline: implications for endogenous biosynthesis and formation during ethanol intoxication. In: Collins MA (ed) Aldehyde adducts in alcoholism. Alan R Liss Inc, New York, pp 145–160
Bosin TR (1978) Serotonin metabolism. In: Essman WB (ed) Serotonin in health and disease, vol 1. Spectrum Publ, New York, pp 181–300
Buckholtz NS (1980) Neurobiology of tetrahydro-β-carbolines. Life Sci 27:893–903
Eriksson CJP, Dietrich RA (1980) Evidence against a biphasic effect of acetaldehyde on voluntary ethanol consumption in rats. Pharmacol Biochem Behav 13 (Suppl 1):191–296
Greiner B, Rommelspacher H (1984) New metabolic pathways of tetrahydronorharmane (tetrahydro-β-carboline) in rats. Naunyn-Schmiedeberg's Arch Pharmacol 325:349–355
Ho BT, Taylor D, Walker KE, McIsaac W (1972) Metabolism of 6-methoxytetrahydro-β-carboline in rats. Xenobiotica 2:349–362
Holman RB, Elliott GR, Faull F, Barchas JD (1980) Tryptolines: The role of indoleamine-aldehyde condensation products in the effects of alcohol. In: Sander M (ed) Psychopharmacology of alcohol. Raven Press, New York, pp 155–169
Jepson JB, Zaltzman P, Udenfriend S (1962) Microsomal hydroxylation of tryptamine, indoleacetic acid and related compounds, to 6-hydroxy derivatives. Biochim Biophys Acta 62:91–102
Johnson JV, Yost RA, Beck O, Faull KF (1985) The use of tandem mass spectrometry for the identification and quantitation of tryptolines (tetrahydro-β-carbolines) in tissue extracts. In: Collins MA (ed) Acetaldehyd adducts in alcoholism. Alan R Liss Inc., New York, pp 145–160
Kopin IJ, Pare CMB, Axelrod J, Weissbach H (1961) The fate of melatonin in animals. J Biol Chem 236:3072–3075
Kveder S, McIsaac WM (1961) The metabolism of melatonin (N-acetyl-5-methoxytryptamine) and 5-methoxytryptamine. J Biol Chem 236:3214–3220
Lemberger L, Axelrod J, Kopin IJ (1971) The disposition and metabolism of tryptamine and the in vivo formation of 6-hydroxytryptamine in the rabbit. J Pharmacol Exp Ther 177:169–176
Le Men J, Fan C (1959) Separation des stéréoisomères des esters éthyliques des acides py-tétrahydro-nor-harmane 5-carboxylique. Bull Soc Chim France 1866–1871
Repke DB, Ferguson WJ (1982) Synthesis of 5-methoxy- and 5-hydroxy-1,2,3,4-tetrahydro-9H-pyrido(3,4-b) in doles. J Heterocyclic Chem 19:845–848
Shaw GJ, Wright GI, Milne GWA (1976) The synthesis of α,α,β,β-d4-serotonin. Biomed Mass Spectrom 3:146–148
Slotkin T, DiStefano V (1970) Urinary metabolites of harmine in the rat and their inhibition of monoamine oxidase. Biochem Pharmacol 19:125–131
Spenser ID (1959) A synthesis of harmaline. Can J Chem 37:1851–1858
Szara S, Hearst E (1962) The 6-hydroxylation of tryptamine derivatives: a way of producing psychoactive metabolites. Ann NY Acad Sci 96:134–141
Taborsky RG, McIsaac WM (1964) The synthesis and preliminary pharmacology of some 9H-pyrido(3,4-b)indoles (β-carbolines) and tryptamines related to serotonin and melatonin. J Med Chem 7:135–141
Ung-Chhun N, Cheng BY, Pronger DA, Serrano P, Chavez B, Perez RF, Morales J, Collins MA (1985) Alkaloid adducts in human brain: coexistence of 1-carboxylated and non-carboxylated isoquinolines and β-carbolines in alcoholics and nonalcoholics. In: Collins MA (ed) Aldehyde adducts in alcoholism. Alan R. Liss Inc, New York, pp 125–136
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Beck, O., Faull, K.F. & Repke, D.B. Rapid hydroxylation of methtryptoline (1-methyltetrahydro-β-carboline) in rat: Identification of metabolites by chiral gas chromatography-mass spectrometry. Naunyn-Schmiedeberg's Arch. Pharmacol. 333, 307–312 (1986). https://doi.org/10.1007/BF00512946
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DOI: https://doi.org/10.1007/BF00512946