Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin uptake transporter and the vesicle monoamine transporter

@article{Cozzi2009DimethyltryptamineAO,
  title={Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin uptake transporter and the vesicle monoamine transporter},
  author={Nicholas V Cozzi and Anupama Gopalakrishnan and Lyndsey L. Anderson and Joel T. Feih and Alexander T. Shulgin and Paul F. Daley and Arnold E Ruoho},
  journal={Journal of Neural Transmission},
  year={2009},
  volume={116},
  pages={1591-1599}
}
N,N-dimethyltryptamine (DMT) is a potent plant hallucinogen that has also been found in human tissues. When ingested, DMT and related N,N-dialkyltryptamines produce an intense hallucinogenic state. Behavioral effects are mediated through various neurochemical mechanisms including activity at sigma-1 and serotonin receptors, modification of monoamine uptake and release, and competition for metabolic enzymes. To further clarify the pharmacology of hallucinogenic tryptamines, we synthesized DMT, N… 

Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes

TLDR
All psychoactive tryptamines are 5-HT2A agonists, but5-HT transporter (SERT) activity may contribute significantly to the pharmacology of certain compounds, and in vitro transporter data confirm structure-activity trends for releasers and uptake inhibitors whereby releasers tend to be structurally smaller compounds.

Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens

Metabolites of Tryptamine : Endogenous psychedelic neurotransmitters , and N , N dimethyltryptamine ( DMT ) in explaining a new pathway to produce Serotonin , Melatonin and hallucinations

TLDR
The journey DMT takes from the intracellular makings to the sensory faking’s renown as well as new concepts to explain the chemical pathways and their associated enzymes in the brain are highlighted.

The role of 5-HT2A, 5-HT2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice

TLDR
The 5-HT2AR likely plays a major role in mediating the effects of two tryptamine hallucinogenic drugs and likely modulate the discriminative stimulus effects of both compounds.

The hallucinogenic world of tryptamines: an updated review

TLDR
A comprehensive update on tryptamine hallucinogens, concerning their historical background, prevalence, patterns of use and legal status, chemistry, toxicokinetics, toxicodynamics and their physiological and toxicological effects on animals and humans is provided.

Noncompetitive Inhibition of Indolethylamine-N-methyltransferase by N,N-Dimethyltryptamine and N,N-Dimethylaminopropyltryptamine

TLDR
The demonstration of noncompetitive mechanisms for INMT inhibition implies the presence of an inhibitory allosteric site, which may illuminate new biochemical pathway(s) underlying the biology of INMT.

Hallucinogen-Like Action of the Novel Designer Drug 25I-NBOMe and Its Effect on Cortical Neurotransmitters in Rats

TLDR
The data from this study suggest that hallucinogenic activity of 25I-NBOMe seems to be related with the increase in extracellular GLU level-mediated via cortical 5-HT2A receptors, and may modulate its effect on neurotransmitters and HTR.

Abuse Liability Profile of Three Substituted Tryptamines

TLDR
DIPT and 5-MeO-DET may have abuse liability similar to known hallucinogens and may be hazardous because high doses produced activity and lethality, but were not similar to those of psychostimulants.

Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens

N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function

This report provides a historical overview of research concerning the endogenous hallucinogen N, N-dimethyltryptamine (DMT), focusing on data regarding its biosynthesis and metabolism in the brain
...

References

SHOWING 1-10 OF 69 REFERENCES

Differential interactions of dimethyltryptamine (DMT) with 5-HT1A and 5-HT2 receptors.

Interactions of tryptamine derivatives with serotonin transporter species variants implicate transmembrane domain I in substrate recognition.

TLDR
A critical role for TMD I residues is supported in defining shared aspects of SERT substrate and antagonist recognition as well as species-specific recognition of citalopram and mazindol.

Serotonin receptor binding affinities of several hallucinogenic phenylalkylamine and N,N-dimethyltryptamine analogues.

TLDR
The most behaviorally potent analogues examined, DOB, DOM, and 5-methoxy-N,N-dimethyltryptamine, were found to possess rather high affirmities for the 5-HT receptors of the model system.

The Hallucinogen N,N-Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator

The sigma-1 receptor is widely distributed in the central nervous system and periphery. Originally mischaracterized as an opioid receptor, the sigma-1 receptor binds a vast number of synthetic

Endogenous psychoactive tryptamines reconsidered: an anxiolytic role for dimethyltryptamine.

Transmembrane Domain I Contributes to the Permeation Pathway for Serotonin and Ions in the Serotonin Transporter

TLDR
The ability of the D98E mutant to modulate selective aspects of substrate recognition, to perturb ion dependence as well as modify substrate-induced currents, suggests that transmembrane domain I plays a critical role in defining the permeation pathway of biogenic amine transporters.
...