Agonist Properties of N,N-Dimethyltryptamine at Serotonin 5-HT2A and 5-HT2C Receptors

@article{Smith1998AgonistPO,
  title={Agonist Properties of N,N-Dimethyltryptamine at Serotonin 5-HT2A and 5-HT2C Receptors},
  author={Randy L. Smith and Herv{\'e} Canton and Robert John Barrett and Elaine sanders-Bush},
  journal={Pharmacology Biochemistry and Behavior},
  year={1998},
  volume={61},
  pages={323-330}
}

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References

SHOWING 1-10 OF 21 REFERENCES
Lysergic acid diethylamide and 2,5-dimethoxy-4-methylamphetamine are partial agonists at serotonin receptors linked to phosphoinositide hydrolysis.
TLDR
LSD partially antagonized the effect of 5-HT in the choroid plexus, consistent with a partial agonist effect at the 5- HT-1c receptor in this tissue.
Reciprocal binding properties of 5-hydroxytryptamine type 2C receptor agonists and inverse agonists.
TLDR
5-HT2C receptor neutral antagonists exhibited functional and receptor binding properties consistent with those of classical receptor antagonists, however, 5-HT 2C receptor inverse agonists displayed functional and receptors binding properties that were opposite those of agonists.
Characterization of the 5-HT2 receptor antagonist MDL 100907 as a putative atypical antipsychotic: behavioral, electrophysiological and neurochemical studies.
TLDR
The data indicate that MDL 100,907 has a clozapine-like profile of potential antipsychotic activity with low extrapyramidal sid-effect liability.
Antagonism of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane stimulus with a newly identified 5-HT2- versus 5-HT1C-selective antagonist.
TLDR
It would appear that the DOM stimulus is primarily a 5-HT2-mediated, and not 5- HT1C- mediated, phenomenon, and compound 26 may find application in other pharmacologic investigations where spiperone may not be a suitable antagonist.
Pharmacological activity of the isomers of LY53857, potent and selective 5-HT2 receptor antagonists.
TLDR
The present study investigated the activities of the diastereomers of LY53857 and found that a similar profile of selectivity was demonstrated for each of the isomers studied, with the meso mixture of isomers being slightly less potent than the SS- and RR-isomers after p.o.v. administration of serotonin.
Human psychopharmacology of N,N-dimethyltryptamine
  • R. Strassman
  • Psychology, Biology
    Behavioural Brain Research
  • 1995
Neurochemical and behavioral evidence that quipazine-ketanserin discrimination is mediated by serotonin2A receptor.
TLDR
The combined results from the substitution, antagonism and ex vivo receptor autoradiographic studies suggest that the discriminative stimuli of quipazine and ketanserin are mediated at least in part by the 5-HT2A receptor.
Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects.
TLDR
Dimethyltryptamine can be administered safely to experienced hallucinogen users and dose-response data generated for several measures hypothesized under serotonergic modulatory control may prove useful in psychopharmacological investigations of drug-induced and endogenous alterations in brain function.
...
...