Serotonin 2A Receptor (5-HT2AR) Activation by 25H-NBOMe Positional Isomers: In Vitro Functional Evaluation and Molecular Docking.
Eline Pottie, Olga V. Kupriyanova, Asher L. Brandt, R. Laprairie, Vadim A Shevyrin, Christophe P Stove
ACS Pharmacology & Translational Science February 25, 2021 DOI: 10.1021/acsptsci.0c00189 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro study Peer reviewed |
|---|---|
| Intervention | 25H-NBOMe positional isomers |
| Topics | Serotonin |
| Key points | The positioning of methoxy groups on the phenethylamine moiety of 25H-NBOMe isomers affects their functional activity at the serotonin 2A receptor. |
Abstract
Serotonergic psychedelics are defined as compounds having serotonin 2A receptor (5-HT2AR) activation as an important pharmacological mechanism. These compounds include the phenylalkylamine class, containing substances with e.g. 2C-X structures (phenethylamines) or their N-methoxybenzyl analogues (NBOMes). Besides their abuse potential, psychedelics are increasingly recognized for having therapeutic benefits. However, many psychedelics remain incompletely characterized, even concerning their structure-activity relationships. Here, five positional isomers of 25H-NBOMe, with two methoxy groups on the different positions of the phenyl ring of the phenethylamine moiety, were subjected to split-nanoluciferase assays assessing the in vitro recruitment of cytosolic proteins to the 5-HT2AR. Furthermore, molecular docking at the 5-HT2AR allowed estimation of which residues interact with the specific isomers' methoxy groups. Although the optimal substitution pattern of N-unsubstituted phenylalkylamines has been extensively studied, this is the first comparative evaluation of the functional effects of the positioning of the methoxy groups in the phenethylamine moiety of NBOMes.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
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- Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants Chemical Reviews November 30, 2023
- Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans Molecules April 22, 2021
- Discovery of β-Arrestin-Biased 25CN-NBOH-Derived 5-HT2A Receptor Agonists. Journal of Medicinal Chemistry September 22, 2022
- Comparative Pharmacological Effects of Lisuride and Lysergic Acid Diethylamide Revisited. ACS Pharmacology & Translational Science March 8, 2024
- Structure-Activity Assessment and In-Depth Analysis of Biased Agonism in a Set of Phenylalkylamine 5-HT2A Receptor Agonists. ACS Chemical Neuroscience August 2, 2023
and 13 more in the library
Cites 14
- Designer drugs: mechanism of action and adverse effects Archives of Toxicology April 1, 2020
- Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs). Neuropharmacology December 1, 2015
- Therapeutic Applications of Classic Hallucinogens. Current Topics in Behavioral Neurosciences 2018
- DARK Classics in Chemical Neuroscience: NBOMes ACS Chemical Neuroscience October 28, 2019
- Serotonergic Psychedelics: Experimental Approaches for Assessing Mechanisms of Action Handbook of experimental pharmacology 2018
and 9 more in the library