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LPH-5 (drug)

Clinical data
Drug class	Serotonergic psychedelic; Hallucinogen; Antidepressant; Selective 5-HT2A receptor agonist
ATC code	None
Legal status
Legal status	In General Unscheduled
Identifiers
IUPAC name (S)-3-(2,5-Dimethoxy-4-(trifluoromethyl)phenyl)piperidine
CAS Number	2641630-97-7
PubChem CID	156337168
Chemical and physical data
Formula	C14H18F3NO2
Molar mass	289.298 g·mol
3D model (JSmol)	Interactive image
SMILES COC1=CC(2()CNCCC2)=C(OC)C=C1C(F)(F)F
InChI InChI=InChI=1S/C14H18F3NO2/c1-19-12-7-11(14(15,16)17)13(20-2)6-10(12)9-4-3-5-18-8-9/h6-7,9,18H,3-5,8H2,1-2H3/t9-/m1/s1 Key:NZKYTYHIERLZBG-SECBINFHSA-N

LPH-5 is a psychedelic discovered by Emil Marcher-Rørsted, Jesper L. Kristensen and Anders A. Jensen at Danish biopharmaceutical company Lophora. It is a conformationally-restricted derivative of the phenethylamine 2C-TFM, also a hallucinogen, and acts as a potent agonist of the 5-HT_2A receptor (EC₅₀ = 3.2 nM, E_max = 78%). It shows 10- to 100-fold selectivity for the 5-HT_2A receptor over the 5-HT_2B and 5-HT_2C receptors and, along with related compounds like 25CN-NBOH, is said to be one of the few truly selective 5-HT_2A receptor agonists. LPH-5 is expected to avoid the cardiac risks of 5-HT_2B receptor activation.

LPH-48, an analogue of LPH-5 that likewise acts as a selective serotonin 5-HT_2A receptor agonist and psychedelic hallucinogen and shows similar characteristics but has a shorter duration of action, is also under development by Lophora.

See also

• 2C-B-PP
• 2C-TFM
• CYB-210010
• OSU-6162
• TCB-2
• ZC-B

References

1. ^ 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-HT_2A Receptor Agonists". Journal of Medicinal Chemistry. 67 (9): 7224–7244. doi:10.1021/acs.jmedchem.4c00082. PMC 11089506. PMID 38648420.
2. ^ 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.
3. 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. 
4. 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.
5. "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
6. 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.

• Drugs not assigned an ATC code
• 3-Piperidinyl compounds
• Experimental antidepressants
• Experimental hallucinogens
• Phenol ethers
• Psychedelic phenethylamines
• Selective 5-HT2A receptor agonists
• Trifluoromethyl compounds