LPH-5 is a psychedelic discovered by Emil Marcher-Rørsted, Jesper L. Kristensen and Anders A. Jensen at Danish biopharmaceutical company Lophora.[1][2] It is a conformationally-restricted derivative of the phenethylamine 2C-TFM, also a hallucinogen, and acts as a potent agonist of the 5-HT2A receptor (EC50 = 3.2 nM, Emax = 78%).[3] It shows 10- to 100-fold selectivity for the 5-HT2A receptor over the 5-HT2B and 5-HT2C receptors and, along with related compounds like 25CN-NBOH, is said to be one of the few truly selective 5-HT2A receptor agonists.[1][2] LPH-5 is expected to avoid the cardiac risks of 5-HT2B receptor activation.[4]
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| Drug class | Serotonergic psychedelic; Hallucinogen; Antidepressant; Selective 5-HT2A receptor agonist |
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| Formula | C14H18F3NO2 |
| Molar mass | 289.298 g·mol−1 |
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LPH-48, an analogue of LPH-5 that likewise acts as a selective serotonin 5-HT2A receptor agonist and psychedelic hallucinogen and shows similar characteristics but has a shorter duration of action, is also under development by Lophora.[5][6]
See also
editReferences
edit- ^ a b M Ro Rsted E, Jensen AA, Smits G, Frydenvang K, Kristensen JL (May 2024). "Discovery and Structure-Activity Relationships of 2,5-Dimethoxyphenylpiperidines as Selective Serotonin 5-HT2A Receptor Agonists". Journal of Medicinal Chemistry. 67 (9): 7224–7244. doi:10.1021/acs.jmedchem.4c00082. PMC 11089506. PMID 38648420.
- ^ a b Jensen AA, Cecchi CR, Hibicke M, Bach AH, Kaadt E, Marcher-Rorsted E, et al. (22 April 2024). "The selective 5-HT 2A receptor agonist LPH-5 induces persistent and robust antidepressant-like effects in rodents". bioRxiv. doi:10.1101/2024.04.19.590212.
- ^ US 2021/0137908, Kristensen JL, Jensen AA, Märcher-Rørsted E, "5-HT2A Agonists for Use in Treatment of Depression.", published 13 May 2021, assigned to Lophora ApS.
- ^ Peplow M (2024). "Next-generation psychedelics: should new agents skip the trip?". Nature Biotechnology. 42 (6): 827–830. doi:10.1038/s41587-024-02285-1. ISSN 1087-0156.
Another problem is that some classical psychedelics are also agonists of the 5-HT2B receptor, which is expressed in heart tissue and can cause long-term cardiac problems. Kristensen's company Lophora aims to solve that with its lead compound LPH-5, a phenylethylamine derivative with an extra molecular ring that makes it less flexible. LPH-5 has a 60-fold higher selectivity for 5-HT2A over 5-HT2B.
- ^ "LPH 48". AdisInsight. 22 May 2024. Retrieved 30 October 2024.
LPH 48 is a ligand therapeutic which has a similar pharmacological profile as psilocybin with superior selectivity and shorter duration, being developed by [...]
- ^ Lophora (31 May 2024). "Lophora Submits Clinical Trial Authorisation (CTA) Application to the French Medicines Agency (ANSM) for Lead CNS Drug LPH-5" (PDF). Retrieved 30 October 2024.
About LPH-48: LPH-48 is a shorter acting direct analog of LPH-5 with similar optimized characteristics and safety profile, but with a shorter duration of action. LPH-48 is designed as a fast-follower that shows significantly faster metabolism, indicating a shorter duration of action in man. LPH-48 is a representative of the same proprietary compound class as LPH-5 and is therefore endowed with the same optimized characteristics including favorable drug-like properties and a safe pharmacological profile.