LPH-5, also known as(S)-3-(2,5-dimethoxy-4-(trifluoromethyl)phenyl)piperidine, is apsychedelic drug discovered by Emil Marcher-Rørsted, Jesper L. Kristensen and Anders A. Jensen at Danish biopharmaceutical company Lophora.[1][2] It is aconformationally-restrictedderivative of thephenethylamine2C-TFM, also a hallucinogen, and acts as apotentagonist of the5-HT2A receptor (EC50 = 3.2 nM, Emax = 78%).[3] It shows 10- to 100-foldselectivity for the 5-HT2A receptor over the5-HT2B and5-HT2C receptors and, along with related compounds like25CN-NBOH, is said to be one of the few truly selective 5-HT2A receptor agonists.[1][2] LPH-5 is expected to avoid thecardiac risks of 5-HT2B receptor activation.[4]
LPH-48, ananalogue of LPH-5 that likewise acts as a selective serotonin 5-HT2A receptor agonist and psychedelic hallucinogen and shows similar characteristics but has a shorterduration of action, is also under development by Lophora.[5][6]
^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.ISSN1087-0156.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. Retrieved30 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). Retrieved30 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.
