Chemistry:Remlifanserin

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Remlifanserin (INN;[1] developmental code name ACP-204) is a selective serotonin 5-HT2A receptor inverse agonist which is under development for the treatment of Alzheimer's disease psychosis.[2][3][4][5][6][7] It is taken by mouth.[2]

The drug is an improved follow-up compound to the earlier drug pimavanserin (Nuplaizid; ACP-103).[4] It is more potent and selective than pimavanserin as a serotonin 5-HT2A receptor inverse agonist.[8] Remlifanserin shows 32- to 123-fold selectivity for antagonism and inverse agonism of the serotonin 5-HT2A receptor over the serotonin 5-HT2C receptor depending on the bioassay.[8][9] For comparison, pimavanserin's selectivity was 8- to 37-fold depending on the assay.[8] Remlifanserin shows very low affinity for the serotonin 5-HT2B receptor compared to the serotonin 5-HT2A and 5-HT2C receptors.[8] It is expected to have less hERG inhibition and QT prolongation than pimavanserin.[8][9] The drug blocks the head-twitch response induced by the serotonergic psychedelic DOI and the hyperlocomotion induced by the NMDA receptor antagonist dizocilpine (MK-801) in rodents.[8] It has a several-fold shorter half-life than pimavanserin (17.5–19.8 hours vs. 57 hours, respectively).[9][10][11]

Remlifanserin is under development by Acadia Pharmaceuticals.[2][3] As of January 2025, it is in phase 3 clinical trials.[2][3] Some of its clinicaltrials.gov identifier(s) (nct number) are NCT06159673, NCT07029581, NCT06194799, NCT07095465.[12]

See also

References

  1. ↑ "Proposed INN: List 131 International Nonproprietary Names for Pharmaceutical Substances (INN)". WHO Drug Information 38 (2): 421. 2024. https://cdn.who.int/media/docs/default-source/international-nonproprietary-names-(inn)/pl131.pdf#page=187. "remlifanserin N'-{[4-(cyclopropyloxy)phenyl]methyl}-N-[(2,4- difluorophenyl)methyl]-N-(1-methylpiperidin-4-yl)urea serotonin receptor (5-HT2A) inverse agonist [...] C24H29F2N3O2 2289704-13-6 [...]". 
  2. ↑ 2.0 2.1 2.2 2.3 "ACP 204". 23 January 2025. https://adisinsight.springer.com/drugs/800069816. 
  3. ↑ 3.0 3.1 3.2 "Delving into the Latest Updates on ACP-204 with Synapse". 4 February 2025. https://synapse.patsnap.com/drug/f36f15c4eb8b452aaa4b0dbc37561fdc. 
  4. ↑ 4.0 4.1 "ACP-204". 5 February 2024. https://www.alzforum.org/therapeutics/acp-204. 
  5. ↑ "Emerging Pharmacological Approaches for Psychosis and Agitation in Alzheimer's Disease". CNS Drugs 39 (2): 143–160. February 2025. doi:10.1007/s40263-024-01133-9. PMID 39623197. 
  6. ↑ "Overview of Psychiatric Medications in the Pipeline in Phase III Trials as of June 1, 2024: A Systematic Review". Innovations in Clinical Neuroscience 21 (7–9): 27–47. 2024. PMID 39329027. 
  7. ↑ "Future Therapeutic Strategies for Alzheimer's Disease: Focus on Behavioral and Psychological Symptoms". International Journal of Molecular Sciences 25 (21). October 2024. doi:10.3390/ijms252111338. PMID 39518892. 
  8. ↑ 8.0 8.1 8.2 8.3 8.4 8.5 "ACNP 63rd Annual Meeting: Poster Abstracts P305-P608: P497. Nonclinical Characterization of ACP-204, a Novel Second Generation 5-HT2A Inverse Agonist". Neuropsychopharmacology 49 (Suppl 1): 236–417 (346–347). December 2024. doi:10.1038/s41386-024-02012-z. PMID 39643634. https://acadia.com/en-us/pdf/healthcare-professionals/scientific-publications/congress-materials/ACNP_ACP-204_Non-clinical_Poster_FINAL.pdf. 
  9. ↑ 9.0 9.1 9.2 "Nonclinical characterization of ACP-204, a novel selective serotonin receptor subtype 2A receptor inverse agonist". J Pharmacol Exp Ther 393 (6). May 2026. doi:10.1016/j.jpet.2026.104932. PMID 42208178. 
  10. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named DarwishFengDirks2025
  11. ↑ "Population pharmacokinetics of remlifanserin (ACP-204), a serotonin 2A receptor inverse agonist". Alzheimers Dement (N Y) 12. 2026. doi:10.1002/trc2.70254. PMID 42080000. 
  12. ↑ ACADIA Pharmaceuticals Inc. (2025-02-21). A Master Protocol for Three Independent, Seamlessly Enrolling, Double-blind, Placebo-controlled Efficacy and Safety Studies of ACP-204 in Adults with Alzheimer's Disease Psychosis (Report). clinicaltrials.gov. https://clinicaltrials.gov/study/NCT06159673. 



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