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. 

Tryptoline formation by a preparation from brain with 5-methyltetrahydrofolic acid and tryptamine.

An enzymatic preparation from human brain converts tryptamine to tryptoline (9H-1,2,3, 4-tetrahydropyrido[3,4-b]indole) and N-methyltryptamine and 5-hydroxytryptamine yield 1-mthyltryptoline and 5,hydroxyTryptoline, respectively.

Degradation of tryptamine in pig brain: identification of a new condensation product.

AN ASSAY PROCEDURE FOR TRYPTAMINE IN BRAIN AND SPINAL CORD USING ITS [3H]DANSYL DERIVATIVE

The brain content of tryptamine increased after MAO inhibition and was not significantly further increased when tryptophan loading was combined with inhibition of MAO and/or tryptphan 5‐hydroxylase, and the tryptamines concentration of spinal cord exceeded that of brain and increased rapidly after death.

THE DISTRIBUTION AND PROPERTIES OF THE NONSPECIFIC N‐METHYLTRANSFERASE IN BRAIN

Enzymatic activity is unevenly distributed in the brain with the highest activity in the cerebral cortex and striaturn of the rat and in the subcortical white matter in man.

ENZYMATIC N‐METHYLATION OF INDOLEAMINES BY MAMMALIAN BRAIN: FACT OR ARTEFACT?

Examination of the reaction products by means of exhaustive thin‐layer chromatographic analysis failed to reveal evidence of significant N‐ methylation of tryptamine or N‐methyltryptamine by S‐adenosylmethionine, but N‐methylation of indoleamine was reproducibly demonstrable.

Indolethylamine-N-methyltransferase in developing rabbit lung.

The activity of indolethylamine-N-methyltransferase (INMT) from the rabbit lung is relatively high in the newborn and increases rapidly after birth, attaining its maximum level at 15 days of age.
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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 also

The enzymatic N-methylation of serotonin and other amines.

  • J. Axelrod
  • Biology, Chemistry
    The Journal of pharmacology and experimental therapeutics
  • 1962
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.

Purification and properties of phenylethanolamine-N-methyl transferase.

  • J. Axelrod
  • Biology, Chemistry
    The Journal of biological chemistry
  • 1962
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.

Detection of Psychotomimetic N,N-Dimethylated Indoleamines in the Urine of Four Schizophrenic Patients

On the basis of their previous work indicating that tryptamine appeared in increased concentrations in the urine before and during the activation of psychotic symptoms, they suggested that under loading conditions the formation of various N,N-dimethylated indoleamines might be facilitated in the body.

SOME OBSERVATIONS ON THE ESTIMATION OF TRYPTAMINE IN TISSUES

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.

A fluorometric procedure for the measurement of tryptamine in tissues.

  • S. HessS. Udenfriend
  • Biology, Chemistry
    The Journal of pharmacology and experimental therapeutics
  • 1959
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.

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.

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.

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 in