Extensive rigid analogue design maps the binding conformation of potent N-benzylphenethylamine 5-HT2A serotonin receptor agonist ligands.
Jose I Juncosa, Martin Hansen, Lisa A Bonner, Juan Pablo Cueva, Rebecca Maglathlin, John D. Mccorvy, Danuta Marona‐lewicka, Markus A Lill, David E Nichols
ACS Chemical Neuroscience January 16, 2013 DOI: 10.1021/cn3000668 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | Serotonin |
| Key points | Proposes that the compound (S,S)-9b, with 124-fold selectivity for 5-HT(2A) over 5-HT(2C), is the most selective 5-HT(2A) receptor agonist ligand currently known. |
Abstract
Based on the structure of the superpotent 5-HT(2A) agonist 2-(4-bromo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine, which consists of a ring-substituted phenethylamine skeleton modified with an N-benzyl group, we designed and synthesized a small library of constrained analogues to identify the optimal arrangement of the pharmacophoric elements of the ligand. Structures consisted of diversely substituted tetrahydroisoquinolines, piperidines, and one benzazepine. Based on the structure of (S,S)-9b, which showed the highest affinity of the series, we propose an optimal binding conformation. (S,S)-9b also displayed 124-fold selectivity for the 5-HT(2A) over the 5-HT(2C) receptor, making it the most selective 5-HT(2A) receptor agonist ligand currently known.
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Citations in the library
Cited by 35
- Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. Neuropharmacology May 1, 2020
- Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential. Nature Communications December 15, 2023
- Synthesis and structure-activity relationships of N-benzyl phenethylamines as 5-HT2A/2C agonists. ACS Chemical Neuroscience March 19, 2014
- Pharmacology and Toxicology of N-Benzylphenethylamine ("NBOMe") Hallucinogens. Current Topics in Behavioral Neurosciences 2017
- N-Benzyl-5-methoxytryptamines as Potent Serotonin 5-HT2 Receptor Family Agonists and Comparison with a Series of Phenethylamine Analogues. ACS Chemical Neuroscience July 15, 2015
and 30 more in the library
Cites 3
- Differential phospholipase C activation by phenylalkylamine serotonin 5‐HT2Areceptor agonists Journal of Neurochemistry November 8, 2005
- Dopamine D4 receptor involvement in the discriminative stimulus effects in rats of LSD, but not the phenethylamine hallucinogen DOI. Psychopharmacology April 2009
- Role of the serotonin 5-HT(2A) receptor in learning. Learning & Memory September 1, 2003