ACS Omega
May 13, 2026
Darío Martínez-afani, Breno A. Soares, Jaime Mella-Raipán et al.
1 citation
High Resolution Image Download MS PowerPoint Slide Serotonin 5-HT 2 receptor ligands have attracted the attention of medicinal chemists for the last half-century, first as hallucinogens and later for their antipsychotic, appetite suppressant, antiaddictive and antidepressant potential. Unlike the very potent N -benzylphenethylamine derivatives that include the abundantly studied NBOMe drugs, N...
ACS Chemical Neuroscience
March 20, 2026
E. Pottie, Emma Vertriest, Darío Martínez-afani et al.
N-Benzyl-derived phenethylamines are highly active (psychedelic) 5-HT2AR (serotonin 2A receptor) agonists used as biochemical tools and on the drug market. The impact of adding an N-benzyl substituent to the tryptamine core structure has scarcely been studied. A recent systematic exploration of N-benzyl-substituted (5-MeO-)tryptamines revealed a surprisingly low activity in a Ca2+ mobilization...
Molecular Psychiatry
November 14, 2025
Núria Nadal‐gratacós, Pol Puigseslloses, Laura Hernández‐guzmán et al.
Psychedelics have garnered significant interest for their therapeutic potential in mental health conditions such as depression, anxiety, and post-traumatic stress disorder. While research has primarily focused on well-studied psychedelics, phenethylamine derivatives have also gathered interest for their potential therapeutic applications. Thus, this study aims to investigate the pharmacological...
Molecular Psychiatry
November 5, 2025
Dino Luethi, Grant C. Glatfelter, Eline Pottie et al.
1 citation
Abstract Various ring-substituted α-methylphenethylamines (i.e., amphetamines) produce psychedelic-like effects that are primarily mediated by activity at 5-hydroxytryptamine 2A (5-HT 2A ) receptors. Small lipophilic substituents at the 4-position of the 2,5-dimethoxyamphetamine core structure can greatly enhance the clinical potency of such derivatives. Here, we studied the effects of various...
Molecular Psychiatry
October 21, 2025
Pol Puigseslloses, Núria Nadal‐gratacós, Berta Fumàs et al.
1 citation
Current first-line antidepressants, such as selective serotonin reuptake inhibitors (SSRI), often present a delayed onset of action and fail to effectively treat a large proportion of patients, leaving a gap in the treatment of mood disorders. Psychedelics have recently emerged as promising alternatives due to their ability to produce fast-acting antidepressant effects through neuroplastic...
Journal of Medicinal Chemistry
June 18, 2025
Alexandra Sink, Eline Pottie, Samuel J Carter et al.
2 citations
The serotonin 2A receptor (5-HT2AR) modulates various neurotransmitter systems and is implicated in psychiatric disorders, including depression and schizophrenia. Despite progress, the detailed mechanisms of signaling at the 5-HT2AR and its therapeutic implications remain unclear, warranting further exploration. Overcoming the limitations of conventional pharmacology, photopharmacology...
Emerging Trends in Drugs, Addictions, and Health
December 14, 2024
Eline Pottie, Grant C. Glatfelter, Michael H. Baumann et al.
Introduction: Serotonergic psychedelics induce their characteristic subjective effects via activation of the serotonin 2A receptor (5-HT2AR). This structurally diverse class of drugs includes ergolines (e.g., LSD), phenethylamines (e.g., mescaline), and tryptamines (e.g., psilocin), all of which have NPS analogues that have emerged on recreational drug markets. Importantly, certain ergolines...
ACS Pharmacology & Translational Science
March 8, 2024
Grant C. Glatfelter, Eline Pottie, John S. Partilla et al.
28 citations
Lisuride is a non-psychedelic serotonin (5-HT) 2A receptor (5-HT2A) agonist and analogue of the psychedelic lysergic acid diethylamide (LSD). Lisuride also acts as an agonist at the serotonin 1A receptor (5-HT1A), a property known to counter psychedelic effects. Here, we tested whether lisuride lacks psychedelic activity due to a dual mechanism: (1) partial agonism at 5-HT2A and (2) potent...
ACS Chemical Neuroscience
August 2, 2023
Eline Pottie, Christian B M Poulie, Icaro A Simon et al.
25 citations
Serotonergic psychedelics are described to have activation of the serotonin 2A receptor (5-HT2A) as their main pharmacological action. Despite their relevance, the molecular mechanisms underlying the psychedelic effects induced by certain 5-HT2A agonists remain elusive. One of the proposed hypotheses is the occurrence of biased agonism, defined as the preferential activation of certain...
Archives of Toxicology
May 1, 2023
Marie H Deventer, Mattias Persson, Antonio Laus et al.
7 citations
New psychoactive substances (NPS) are introduced on the illicit drug market at a rapid pace. Their molecular targets are often inadequately elucidated, which contributes to the delayed characterization of their pharmacological effects. Inspired by earlier findings, this study set out to investigate the µ opioid receptor (MOR) activation potential of a large set of psychedelics, substances which...
ACS Pharmacology & Translational Science
November 2, 2022
Eline Pottie, Marilyn Naeem, Vamshikrishna Reddy Sammeta et al.
91 citations
4-Phosphoryloxy-N,N-dimethyltryptamine (psilocybin) is a naturally occurring tertiary amine found in many mushroom species. Psilocybin is a prodrug for 4-hydroxy-N,N-dimethyltryptamine (psilocin), which induces psychedelic effects via agonist activity at the serotonin (5-HT) 2A receptor (5-HT2A). Several other 4-position ring-substituted tryptamines are present in psilocybin-containing...
Journal of Medicinal Chemistry
September 22, 2022
Christian B M Poulie, Eline Pottie, Icaro A Simon et al.
32 citations
The serotonin 2A receptor (5-HT2AR) is the mediator of the psychedelic effects of serotonergic psychedelics, which have shown promising results in clinical studies for several neuropsychiatric indications. The 5-HT2AR is able to signal through the Gαq and β-arrestin effector proteins, but it is currently not known how the different signaling pathways contribute to the therapeutic effects...
Angewandte Chemie (International ed. in English)
June 27, 2022
Hubert Gerwe, Feng He, Eline Pottie et al.
21 citations
Classical psychedelics are a group of hallucinogens which trigger non-ordinary states of consciousness through activation of the 5-HT2A receptor (5-HT2A R) in the brain. However, the exact mechanism of how 5-HT2A R agonism alters perception remains elusive. When studying receptor signaling, tools which work at the same spatiotemporal resolution as the receptor are exceptionally useful. To...
ACS Pharmacology & Translational Science
February 25, 2021
Eline Pottie, Olga V. Kupriyanova, Asher L. Brandt et al.
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...
Archives of Toxicology
October 1, 2020
Eline Pottie, Annelies Cannaert, Christophe P Stove
correction
It has been brought to the authors' attention that Fig. 1 of "In vitro structure-activity relationship determination of 30 psychedelic new psychoactive substances by means of β-arrestin 2 recruitment to the serotonin 2A receptor" contained a mistake in the structures for 2C-B-FLY and Bromo-DragonFLY. This has now been corrected. The authors apologize for any inconvenience caused.
Biochemical Pharmacology
September 27, 2020
Eline Pottie, P. Dedecker, Christophe P Stove
Psychedelic new psychoactive substances (NPS), compounds exerting their main pharmacological effects through the activation of the serotonin 2A receptor (5-HT2AR), continuously comprise a substantial portion of the reported NPS. However, these substances and their exact mechanism of action, differentiating them from non-psychedelic 5-HT2AR agonists, require further characterization. One...
Archives of Toxicology
July 5, 2020
Eline Pottie, Annelies Cannaert, Christophe P Stove
36 citations
Serotonergic psychedelics, substances exerting their effects primarily through the serotonin 2A receptor (5-HT2AR), continue to comprise a substantial portion of reported new psychoactive substances (NPS). The exact mechanisms of action of psychedelics still remain to be elucidated further, and certain pathways remain largely unexplored on a molecular level for this group of compounds. A...
Analytical Chemistry
November 14, 2019
Eline Pottie, Annelies Cannaert, Katleen van Uytfanghe et al.
29 citations
Classic or serotonergic hallucinogens comprise the third largest number of reported new psychoactive substances (NPS), according to the United Nations Office on Drugs and Crime. While being structurally very divergent, they share activation of the serotonin 2A receptor (5-HT2AR), a G protein-coupled receptor, as their main pharmacological mechanism. Here, we report on the development of a...