Psychotomimetic N-Methylated Tryptamines: Formation in Brain in vivo and in vitro

@article{Saavedra1972PsychotomimeticNT,
  title={Psychotomimetic N-Methylated Tryptamines: Formation in Brain in vivo and in vitro},
  author={Juan M. Saavedra and Julius Axelrod},
  journal={Science},
  year={1972},
  volume={175},
  pages={1365 - 1366}
}
The use of a sensitive enzymatic assay demonstrates that tryptamine occurs normally in rat brain. Intracisternal administration of [14C]tryptamine results in the formation of N-methyl-and dimethyltryptamine(a psychotomimetic compound)in the rat brain. An enzyme that converts tryptamine and N-methyl-tryptamine to N-methyl-and dimethyltryptamine was found to be present in rat and human brain. The N-methylation of tryptamine was inhibited by normally occurring compounds present in rat brain. 

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References

SHOWING 1-10 OF 14 REFERENCES
Enzymatic Formation of Psychotomimetic Metabolites from Normally Occurring Compounds
An enzyme has been found that N-methylates serotonin and tryptamine to psychotomimetic metabolites, bufotenine and N,N-dimethyltryptamine. This enzyme is highly localized in the rabbit lung and alsoExpand
The enzymatic N-methylation of serotonin and other amines.
  • J. Axelrod
  • Chemistry, Medicine
  • The Journal of pharmacology and experimental therapeutics
  • 1962
TLDR
The serotonin methylating enzyme can N-methylate a variety of normally occurring compounds such as dopamine, normetanephrine, metanephine, epinephrine, tyramine, and octopamine as well as a varietyof foreign compounds suchAs ephedrine, amphetamine, aniline, normorphine,normeperidine and nornicotine. Expand
Detection of psychotomimetic N,N-dimethylated indoleamines in the urine of four schizophrenic patients.
TLDR
Increases of urinary bufotenin and other N-methylated indoleamines were observed about two weeks before the mental and behavioural symptoms of the schizophrenic patients worsened, and these elevated levels continued during the period of behavioural exacerbations. Expand
Purification and properties of phenylethanolamine-N-methyl transferase.
  • J. Axelrod
  • Biology, Medicine
  • The Journal of biological chemistry
  • 1962
TLDR
The assay, purification, properties, and distribution of an enzyme, phenylethanolamine-N-methyl transferase, that N-methylates the nitrogen of norepinephrine as well as that of a number of phenylethaolamine derivatives are described. Expand
SOME OBSERVATIONS ON THE ESTIMATION OF TRYPTAMINE IN TISSUES
TLDR
A modification of the original method, incorporating ion‐exchange chromatography, which gives complete separation of these components, and finds tryptamine is found neither in the brain of normal guinea pigs, nor in animals treated with l‐tryptophan. Expand
Inhibition of transmethylations of biogenic amines by S-adenosylhomocysteine. Enhancement of transmethylation by adenosylhomocysteinase.
TLDR
The results show that S-adenosylhomocysteine, a product from S- adenosylmethionine, is a potent inhibitor of these methyltransferases, and that the stimulating factor in brain is an enzyme which enhances transmethylations by hydrolyzing S-ADenosylHomocysteines. Expand
A fluorometric procedure for the measurement of tryptamine in tissues.
  • S. Hess, S. Udenfriend
  • Chemistry, Medicine
  • The Journal of pharmacology and experimental therapeutics
  • 1959
TLDR
A fluorometric method sufficiently sensitive to determine 0.1 to 5 µg of tryptamine in body fluids and tissues is described and can be applied to measure tryptophan in fingertip blood by omitting the extraction. Expand
Pituitary Gland: Enzymic Formation of Methanol from S-Adenosylmethionine
An enzyme has been found that can transform S-adenosylmethionine to methanol and S-adenosylhomocysteine. This enzyme is highly localized in the pituitary gland of several mammalian species.
The effects of pentobarbital on the fate of intracisternally administered norepinephrine-H3.
TLDR
The results of these experiments indicate that the intracisternal injection technique is a rapid, effective and reproducible means of bypassing the blood-brain barrier and labeling endogenous brain stores of norepinephrine. Expand
Effects of Amino Acid Feedings in Schizophrenic Patients Treated with Iproniazid
Large oral doses of individual amino acids were given three or four times daily for periods of 1 week to schizophrenic patients, some of whom were maintained on iproniazid. Marked alterations inExpand
...
1
2
...