Serotonin 5-HT2A receptor antagonist

Serotonin 5-HT2A receptor antagonist
Drug class
Class identifiers
Synonyms5-HT2A antagonist
UseInsomnia, Parkinson's disease psychosis, hallucinogen antidotes (trip killers; against serotonergic psychedelics)
Mechanism of actionSerotonin 5-HT2A receptor antagonism
Biological targetSerotonin 5-HT2A receptor
Legal status
In Wikidata

A serotonin 5-HT2A receptor antagonist, or simply 5-HT2A antagonist, is a drug which acts as an antagonist of the serotonin 5-HT2A receptor.[1] Aside from simple competitive antagonists, these drugs may also be inverse agonists of the serotonin 5-HT2A receptor.[2][3][4][5]

They include non-selective agents like atypical antipsychotics, tricyclic antidepressants (TCAs), tetracyclic antidepressants (TeCAs), and serotonin antagonists and reuptake inhibitors (SARIs) as well as selective agents.[1][6][7] Examples of non-selective serotonin 5-HT2A receptor antagonists include antipsychotics like chlorpromazine, clozapine, olanzapine, quetiapine, risperidone, spiperone (spiroperidol), and ziprasidone; antihistamines like cyproheptadine, hydroxyzine, and LY-2624803; TCAs like amitriptyline, clomipramine, doxepin, imipramine, iprindole, and trimipramine; TeCAs like mianserin, mirtazapine, and esmirtazapine; SARIs and related like trazodone, nefazodone, mepiprazole, niaprazine, and lubazodone; and others like adatanserin, cyclobenzaprine, deramciclane, flibanserin, landipirdine, metergoline, metitepine (methiothepin), MT-1207, opiranserin, pizotifen, roluperidone, and XOB (ASR-6001).[1][6][7] More selective serotonin 5-HT2A receptor antagonists include 4-PhPr-PEA, AMDA, altanserin, butanserin, cinanserin, eplivanserin, fananserin, glemanserin, iferanserin, ketanserin, lidanserin, LY03017, metrenperone, NH130, pelanserin, pimavanserin, pirenperone, pruvanserin, remlifanserin, ritanserin, seganserin, setoperone, and volinanserin.[1][6][7] Peripherally selective or acting serotonin 5-HT2A receptor antagonists are known as well and include BW-501C67, irindalone, naftidrofuryl, sarpogrelate, temanogrel, trelanserin, and xylamidine.[8]

Selective serotonin 5-HT2A receptor antagonists have been studied in the treatment of sleeping disorders such as insomnia, psychiatric disorders such as depression, anxiety, and schizophrenia, and for other indications.[7][9][10] Several selective serotonin 5-HT2A receptor antagonists reached and/or completed phase 3 clinical trials, including and eplivanserin, pimavanserin, pruvanserin, and volinanserin.[9][10][11][12] However, all of them except pimavanserin were discontinued, with pimavanserin having been approved only for the treatment of Parkinson's disease psychosis.[9][13][14] Though not approved for insomnia, selective serotonin 5-HT2A receptor antagonists have been found to improve sleep and sleep quality, including increasing deep slow wave sleep (SWS) without affecting REM sleep.[7][12][6][9][15][16]

Serotonin 5-HT2A receptor antagonists are useful as so-called "trip killers" or hallucinogen antidotes in aborting or shortening the effects of serotonergic psychedelics like psilocybin, LSD, and mescaline.[17][18][19][20] Ketanserin, risperidone, chlorpromazine, and cyproheptadine have all been formally studied and found to be effective for such purposes.[17][18] Ketanserin, pimavanserin, and eplivanserin/volinanserin are under formal development and/or study for this use as well.[21][22][23][24][25][26][27][28] In addition, recreational psychedelic users often use trip killers to abort psychedelic experiences, with frequent use of trazodone, quetiapine, olanzapine, and mirtazapine for these purposes having been documented.[29][30]

See also

References

  1. ^ a b c d Casey AB, Cui M, Booth RG, Canal CE (June 2022). ""Selective" serotonin 5-HT2A receptor antagonists". Biochem Pharmacol. 200 115028. doi:10.1016/j.bcp.2022.115028. PMC 9252399. PMID 35381208.
  2. ^ Berg KA, Harvey JA, Spampinato U, Clarke WP (December 2005). "Physiological relevance of constitutive activity of 5-HT2A and 5-HT2C receptors". Trends Pharmacol Sci. 26 (12): 625–630. doi:10.1016/j.tips.2005.10.008. PMID 16269190.
  3. ^ Berg KA, Harvey JA, Spampinato U, Clarke WP (2008). Physiological and therapeutic relevance of constitutive activity of 5-HT 2A and 5-HT 2C receptors for the treatment of depression. Progress in Brain Research. Vol. 172. pp. 287–305. doi:10.1016/S0079-6123(08)00914-X. ISBN 978-0-444-53235-0. PMID 18772038. {{cite book}}: |journal= ignored (help)
  4. ^ Aloyo VJ, Berg KA, Spampinato U, Clarke WP, Harvey JA (February 2009). "Current status of inverse agonism at serotonin2A (5-HT2A) and 5-HT2C receptors". Pharmacol Ther. 121 (2): 160–173. doi:10.1016/j.pharmthera.2008.10.010. PMID 19109993.
  5. ^ De Deurwaerdère P, Bharatiya R, Chagraoui A, Di Giovanni G (May 2020). "Constitutive activity of 5-HT receptors: Factual analysis". Neuropharmacology. 168 107967. doi:10.1016/j.neuropharm.2020.107967. PMID 31958408.
  6. ^ a b c d Landolt HP, Wehrle R (May 2009). "Antagonism of serotonergic 5-HT2A/2C receptors: mutual improvement of sleep, cognition and mood?". Eur J Neurosci. 29 (9): 1795–1809. doi:10.1111/j.1460-9568.2009.06718.x. PMID 19473234.
  7. ^ a b c d e Teegarden BR, Al Shamma H, Xiong Y (2008). "5-HT(2A) inverse-agonists for the treatment of insomnia". Curr Top Med Chem. 8 (11): 969–976. doi:10.2174/156802608784936700. PMID 18673166.
  8. ^ Baxter G, Kennett G, Blaney F, Blackburn T (March 1995). "5-HT2 receptor subtypes: a family re-united?". Trends Pharmacol Sci. 16 (3): 105–110. doi:10.1016/s0165-6147(00)88991-9. PMID 7792930.
  9. ^ a b c d Vanover KE, Davis RE (2010). "Role of 5-HT2A receptor antagonists in the treatment of insomnia". Nat Sci Sleep. 2: 139–150. doi:10.2147/nss.s6849. PMC 3630942. PMID 23616706.
  10. ^ a b Mestre TA, Zurowski M, Fox SH (April 2013). "5-Hydroxytryptamine 2A receptor antagonists as potential treatment for psychiatric disorders". Expert Opin Investig Drugs. 22 (4): 411–421. doi:10.1517/13543784.2013.769957. PMID 23409724.
  11. ^ Abbas A, Roth BL (December 2008). "Pimavanserin tartrate: a 5-HT2A inverse agonist with potential for treating various neuropsychiatric disorders". Expert Opin Pharmacother. 9 (18): 3251–3259. doi:10.1517/14656560802532707. PMID 19040345. At present, there are three 5-HT 2A antagonists in Phase III trials for treating insomnia (eplivanserin, volinanserin, pruvanserin), and two inverse agonists in Phase II insomnia trials (APD125 and HY10275) [34] .
  12. ^ a b Renger JJ (2008). "Overview of experimental and conventional pharmacological approaches in the treatment of sleep and wake disorders". Curr Top Med Chem. 8 (11): 937–953. doi:10.2174/156802608784936755. PMID 18673164.
  13. ^ Chendo I, Ferreira JJ (October 2016). "Pimavanserin for the treatment of Parkinson's disease psychosis". Expert Opin Pharmacother. 17 (15): 2115–2124. doi:10.1080/14656566.2016.1234609. PMID 27609312.
  14. ^ "ACADIA Pharmaceuticals". AdisInsight. 16 June 2025. Retrieved 16 January 2026.
  15. ^ Monti, J.M. (2010). "Serotonin 5-HT2A receptor antagonists in the treatment of insomnia: present status and future prospects". Drugs of Today. 46 (3): 183–193. doi:10.1358/dot.2010.46.3.1437247. PMID 20467592. Retrieved 16 January 2026.
  16. ^ Dijk DJ (June 2010). "Slow-wave sleep deficiency and enhancement: implications for insomnia and its management". World J Biol Psychiatry. 11 Suppl 1: 22–28. doi:10.3109/15622971003637645. PMID 20509829.
  17. ^ a b Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC 10851641. PMID 37982394.
  18. ^ a b Halberstadt AL, Nichols DE (2020). "Serotonin and serotonin receptors in hallucinogen action". Handbook of the Behavioral Neurobiology of Serotonin. Handbook of Behavioral Neuroscience. Vol. 31. pp. 843–863. doi:10.1016/B978-0-444-64125-0.00043-8. ISBN 978-0-444-64125-0. ISSN 1569-7339. S2CID 241134396.
  19. ^ Canal CE (2018). "Serotonergic Psychedelics: Experimental Approaches for Assessing Mechanisms of Action". New Psychoactive Substances. Handbook of Experimental Pharmacology. Vol. 252. pp. 227–260. doi:10.1007/164_2018_107. ISBN 978-3-030-10560-0. PMC 6136989. PMID 29532180. {{cite book}}: |journal= ignored (help)
  20. ^ Holze F, Singh N, Liechti ME, D'Souza DC (May 2024). "Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile". Biol Psychiatry Cogn Neurosci Neuroimaging. 9 (5): 472–489. doi:10.1016/j.bpsc.2024.01.007. PMID 38301886.
  21. ^ Hallifax, James (30 November 2022). "New MindMed Study Shortens Trip with "LSD-Neutralizer"". Microdose. Retrieved 12 May 2025.
  22. ^ "LSD "off-switch" developed by psychedelic pharmaceutical company". New Atlas. 27 April 2020. Retrieved 12 May 2025.
  23. ^ Becker AM, Klaiber A, Holze F, Istampoulouoglou I, Duthaler U, Varghese N, Eckert A, Liechti ME (February 2023). "Ketanserin Reverses the Acute Response to LSD in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Participants". Int J Neuropsychopharmacol. 26 (2): 97–106. doi:10.1093/ijnp/pyac075. PMC 9926053. PMID 36342343.
  24. ^ Holze F, Vizeli P, Ley L, Müller F, Dolder P, Stocker M, Duthaler U, Varghese N, Eckert A, Borgwardt S, Liechti ME (February 2021). "Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects". Neuropsychopharmacology. 46 (3): 537–544. doi:10.1038/s41386-020-00883-6. PMC 8027607. PMID 33059356.
  25. ^ "Psilocybin Mechanism of Action (MOA)". ClinicalTrials.gov. Retrieved 13 November 2024.
  26. ^ "Eplivanserin/volinanserin". AdisInsight. 15 January 2024. Retrieved 15 January 2026.
  27. ^ Cornall, Jim (15 March 2024). "Reformulating psychedelics for neurodegenerative diseases". Labiotech.eu. Retrieved 15 January 2026.
  28. ^ "Sam Clark: Founder and CEO of Terran Biosciences". Buzzsprout. 31 October 2024. Retrieved 15 January 2026.
  29. ^ Yates G, Melon E (January 2024). "Trip-killers: a concerning practice associated with psychedelic drug use" (PDF). Emerg Med J. 41 (2): 112–113. doi:10.1136/emermed-2023-213377. PMID 38123961.
  30. ^ Suran M (February 2024). "Study Finds Hundreds of Reddit Posts on "Trip-Killers" for Psychedelic Drugs". JAMA. 331 (8): 632–634. doi:10.1001/jama.2023.28257. PMID 38294772.
This article is issued from Wikipedia. The text is available under Creative Commons Attribution-Share Alike 4.0 unless otherwise noted. Additional terms may apply for the media files.