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Emil Märcher-Rørsted

Lophora ApS, 2920 Charlottenlund, Denmark.

4 papers in the library · 35 citations · publishing 2020-2025

Papers

The selective 5-HT2A receptor agonist 25CN-NBOH: structure-activity relationship, in vivo pharmacology, and in vitro and ex vivo binding characteristics of [3H]25CN-NBOH.

Biochemical Pharmacology April 13, 2020 A. Jensen, A. Halberstadt, Emil Märcher-Rørsted et al. 25 citations

Modifications to specific positions on the 25CN-NBOH molecule, a highly selective 5-HT2A receptor agonist, can retain or reduce its activity. Six new analogs were tested; 3′-methyl and fused-ring variants kept high 5-HT2A receptor activity, while 3′-methoxy and 3′-ethyl versions lost binding and potency. All six analogs showed only partial agonism or antagonism. In mice, 25CN-NBOH and a close analog triggered head-twitch responses (a hallmark of 5-HT2A activation) and reduced marble-burying behavior, suggesting potential benefits for cognitive rigidity disorders. A tritium-labeled version of 25CN-NBOH showed high binding affinity and selectivity for 5-HT2A receptors in rat brain tissue, providing a new tool for future receptor studies.

DOI: 10.1016/j.bcp.2020.113979 Medicine Chemistry Psychology

Discovery and Structure–Activity Relationships of 2,5-Dimethoxyphenylpiperidines as Selective Serotonin 5-HT2A Receptor Agonists

Journal of Medicinal Chemistry April 22, 2024 Karla Frydenvang, Emil Märcher-Rørsted, Anders A. Jensen et al. 7 citations

Classical psychedelics like psilocybin, LSD, and DMT show promise for treating depression, anxiety, and substance abuse, but their long-term therapeutic effects remain unclear. A new class of compounds, 2,5-dimethoxyphenylpiperidines, has been discovered as selective serotonin 2A receptor (5-HT2AR) agonists. Structure-activity studies identified LPH-5 [analogue (S)-11] as a selective 5-HT2AR agonist with favorable drug-like properties, offering a potential tool to investigate the receptor's role in persistent therapeutic effects.

DOI: 10.1021/acs.jmedchem.4c00082 Pharmacology 5-HT Receptor Structure–activity relationship Serotonin agonist +1

The Selective Serotonin 5-HT2A Receptor Agonist (S)-3-(2,5-Dimethoxy-4-(trifluoromethyl)phenyl)piperidine (LPH-5) Induces Persistent and Robust Antidepressant-Like Effects in Rodents

ACS Pharmacology & Translational Science May 29, 2025 Meghan Hibicke, Erik Kaadt, Emil Märcher-Rørsted et al. 3 citations

A new compound, LPH-5, acts as a potent partial agonist at the 5-HT2A receptor with high selectivity over related 5-HT2B and 5-HT2C receptors. In rats, LPH-5 induced head-twitch responses and produced both acute and persistent antidepressant-like effects. These findings suggest that selective activation of the 5-HT2A receptor alone can produce antidepressant effects, indicating that this receptor is a key component in the therapeutic action of classical psychedelics like psilocybin and LSD.

DOI: 10.1021/acsptsci.5c00208 Serotonin Antidepressant Piperidine Agonist +4

The selective 5-HT2A receptor agonist LPH-5 induces persistent and robust antidepressant-like effects in rodents

bioRxiv Preprint Server April 19, 2024 Anders A. Jensen, Claudia R. Cecchi, Meghan Hibicke et al. preprint

A new compound called LPH-5 selectively activates the 5-HT2A receptor, unlike classical psychedelics which also affect related receptors. In rats, LPH-5 produced head-twitch responses (a behavioral marker of 5-HT2A activation) at doses of 0.5-1.0 mg/kg and showed antidepressant-like effects in three different rat models: Flinders Sensitive Line rats, adrenocorticotropic hormone-treated Sprague Dawley rats, and a Wistar Kyoto rat model designed to capture long-term antidepressant effects. The findings suggest that selective 5-HT2A receptor activation is sufficient for antidepressant potential, and that LPH-5 or similar selective compounds could represent a new generation of antidepressant drugs derived from psychedelics.

DOI: 10.1101/2024.04.19.590212 Full text