Hallucinogenic drug interactions with neurotransmitter receptor binding sites in human cortex

  title={Hallucinogenic drug interactions with neurotransmitter receptor binding sites in human cortex},
  author={Pamela A. Pierce and Stephen J. Peroutka},
The binding affinities of four hallucinogenic agents were analyzed at nine neurotransmitter binding sites in human cortex. d-Lysergic acid diethylamide (d-LSD), N,N-dimethyltryptamine (DMT), 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and 1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane (DOB) display highest affinity for the recently identified “DOB binding site” labeled by 77Br-R(-)DOB. The phenalkylamines, DOI and DOB, display subnanomolar affinity for the 77Br-R(-)DOB-labeled site… 
Hallucinogen-Like Action of the Novel Designer Drug 25I-NBOMe and Its Effect on Cortical Neurotransmitters in Rats
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.
Receptor Interaction Profiles of 4-Alkoxy-Substituted 2,5-Dimethoxyphenethylamines and Related Amphetamines
4-alkyloxy-substituted 2,5-dimethoxyamphetamines and Phenethylamines share some trends with the many other phenethylamine pharmacophore containing compounds, such as when increasing the size of the 4- substituent and increasing the lipophilicity, the affinities at the 5-HT2A/C subtype also increase, and only weak 5- HT2A or C subtype selectivities were achieved.
Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice
It is confirmed that psilocin acts as an agonist at 5-HT1A, 4-hydroxy-N,N-dimethyltryptamine, and 5- HT2C receptors in mice, whereas the behavioral effects of 1-methylpsilocin indicate that this compound is acting at5-HT2A sites but is inactive at the 5-ht1A receptor.
Tolerance to neurochemical and behavioral effects of the hallucinogen 25I-NBOMe
The findings suggest that multiple injections of 25I-NBOMe induce tolerance to hallucinogenic activity and produce alterations in neurotransmission and anxiety seems to be the result of complex interactions between neurotransmitter pathways.
Towards a biophysical understanding of hallucinogen action
This work describes a qualitative use of the h5-HT2A receptor homology model to provide a molecular basis for the pharmacological characterization of psychoactive phenylalkylamine hallucinogens and a systematic iterative approach to explore several of the receptor-binding interactions observed in virtual docking simulations to the model.
The hallucinogenic world of tryptamines: an updated review
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.
Agonistic Properties of Cannabidiol at 5-HT1a Receptors
These studies demonstrate that CBD is a modest affinity agonist at the human 5-HT1a receptor, and indicate that cannabidiol may have interesting and useful potential beyond the realm of cannabinoid receptors.
Serotonin and serotonin receptors in hallucinogen action
Comparison of the discriminative stimulus effects of dimethyltryptamine with different classes of psychoactive compounds in rats
Like DOM and LSD, DMT seems to produce predominately hallucinogenic-like discriminative stimulus effects and minimal psychostimulant effects, in contrast to MDMA which produced hallucinogen- and psychostIMulant-like effects.


Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents.
Characterization of a novel 3H-5-hydroxytryptamine binding site subtype in bovine brain membranes
  • R. E. Heuring, S. Peroutka
  • Biology, Chemistry
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1987
The data demonstrate the presence of a homogeneous class of 5- HT1 binding sites in bovine caudate that is pharmacologically distinct from previously defined 5-HT1A, 5-ht1B, 5 - HT1C, 4-HT2, 3-HT3 receptor subtypes.
3H-DOB (4-bromo-2,5-dimethoxyphenylisopropylamine) labels a guanyl nucleotide-sensitive state of cortical 5-HT2 receptors.
3H-DOB labels a subset of brain 5-HT2 receptors that has high affinity for agonists as well as antagonists); 3H-ketanserin appears to label both subsets ofbrain 5- HT2 receptors.
Action of psychotogenic drugs on single midbrain raphe neurons.
The results indicate that the indole and phenethylamine psychotogens, which have similar effects on behavior, also have an overlapping although not identical effect on single units in the raphe nuclei.
Multiple serotonin receptors: differential binding of [3H]5-hydroxytryptamine, [3H]lysergic acid diethylamide and [3H]spiroperidol.
It is proposed that [3H]5-HT and[3H]-spiroperidol label distinct populations of serotonin receptors in rat brain, designated 5-HT1 and 5- HT2 receptors, respectively.
Nerve terminal effects of indoleamine psychotomimetics on 5-hydroxytryptamine
  • A. Halaris
  • Biology
    Neuroscience & Biobehavioral Reviews
  • 1983
Effects of the phenethylamine derivatives, BL-3912, fenfluramine, and Sch-12679, in rats trained with LSD as a discriminative stimulus
A variety of drugs may substitute in whole or in part for LSD in LSD-trained rats, and even complete substitution of a drug forLSD in the rat is not necessarily associated with the production by that drug of hallucinations in man.