Eplivanserin, also known by its former developmental code namesSR-46349 andSR-46615 and by its former tentative brand namesCiltyri andSliwens, is aserotonin5-HT2A receptorantagonist which was under development bySanofi Aventis for the treatment of a variety ofmedical conditions but was never marketed.[1][3] It is takenorally.[1]
The drug has been shown toupregulate serotonin 5-HT2A receptor expression, unlike many known serotonin 5-HT2A receptor antagonists, which paradoxically induce receptordownregulation.[10][11] Relatedly, although eplivanserin given acutely can block the head-twitch response induced by various serotonergic drugs, it can also enhance the head-twitch response induced by 5-HTP and psychedelics like DOI when given on a sub-acute basis (given continuously and then withdrawn).[12][13]
Eplivanserin is well-absorbed, with anabsorption of more than 70%.[2] Thetime to peak levels of eplivanserin is 2 to 6hours.[2] Itselimination half-life is relatively long, with an average value of 50hours.[2]
The condensation between 2'-Fluoroacetophenone [445-27-2] (5) &4-hydroxybenzaldehyde [123-08-0] (6) give a chalcone intermediate (also an enone), i.e.CID:53982926 (7).
(2-chloroethyl)dimethylamine (CDMA) &acetone oxime are reacted together to give dimethylaminoacetoxime (DMA acetoxime),CID:16641114 (3).
Convergent synthesis gives the product as a mixture of isomers.
^abcde"Eplivanserin".AdisInsight. 5 November 2023. Retrieved15 January 2026.
^abcde"Method of treating sleep disorders using eplivanserin".Google Patents. 10 November 2009.Eplivanserin or pharmaceutically acceptable salts or esters thereof, in particular hemifumarate salt, is an antagonist of 5HT2A receptors (Journal of Pharmacological Experiment in Therapeutics, (1992), vol. 262 (2), pp. 759-68). Eplivanserin is well absorbed (>70%). Conventional dosage, between 1 and 10 mg, leads to a maximal plasma concentration that is reached between 2 and 6 hours; the half-life time of eplivanserin or pharmaceutically acceptable salts or esters thereof is relatively long, with an average value of 50 hours. Eplivanserin or pharmaceutically acceptable salts or esters thereof is also known to enhance slow wave sleep (SWS) (Neuropsychopharmacology (1999), vol.21 (3), pp. 455-466).
^abTeegarden BR, Al Shamma H, Xiong Y (2008). "5-HT(2A) inverse-agonists for the treatment of insomnia".Current Topics in Medicinal Chemistry.8 (11):969–76.doi:10.2174/156802608784936700.PMID18673166.
^Rinaldi-Carmona M, Congy C, Santucci V, Simiand J, Gautret B, Neliat G, Labeeuw B, Le Fur G, Soubrie P, Breliere JC (August 1992). "Biochemical and pharmacological properties of SR 46349B, a new potent and selective 5-hydroxytryptamine2 receptor antagonist".J Pharmacol Exp Ther.262 (2):759–768.doi:10.1016/S0022-3565(25)10821-5.PMID1501121.
^McDonald LM, Moran PM, Vythelingum GN, Joseph MH, Stephenson JD, Gray JA (September 2003). "Enhancement of latent inhibition by two 5-HT2A receptor antagonists only when given at both pre-exposure and conditioning".Psychopharmacology (Berl).169 (3–4):321–331.doi:10.1007/s00213-002-1173-4.PMID14530903.
^Schreiber R, Brocco M, Audinot V, Gobert A, Veiga S, Millan MJ (April 1995). "(1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane)-induced head-twitches in the rat are mediated by 5-hydroxytryptamine (5-HT) 2A receptors: modulation by novel 5-HT2A/2C antagonists, D1 antagonists and 5-HT1A agonists".J Pharmacol Exp Ther.273 (1):101–112.doi:10.1016/S0022-3565(25)09485-6.PMID7714755.
^Darmani NA, Reeves SL (September 1996). "The mechanism by which the selective 5-HT1A receptor antagonist S-(-) UH 301 produces head-twitches in mice".Pharmacol Biochem Behav.55 (1):1–10.doi:10.1016/0091-3057(96)00072-x.PMID8870031.
^Darmani NA (1998). "The silent and selective 5-HT1A antagonist, WAY 100635, produces via an indirect mechanism, a 5-HT2A receptor-mediated behaviour in mice during the day but not at night. Short communication".J Neural Transm (Vienna).105 (6–7):635–643.doi:10.1007/s007020050085.PMID9826108.
^Rinaldi-Carmona M, Congy C, Simiand J, Oury-Donat F, Soubrie P, Breliere JC, Le Fur G (January 1993). "Repeated administration of SR 46349B, a selective 5-hydroxytryptamine2 antagonist, up-regulates 5-hydroxytryptamine2 receptors in mouse brain".Molecular Pharmacology.43 (1):84–89.doi:10.1016/S0026-895X(25)13451-2.PMID8423772.
^Rinaldi-Carmona M, Congy C, Simiand J, Oury-Donat F, Soubrie P, Breliere JC, Le Fur G (January 1993). "Repeated administration of SR 46349B, a selective 5-hydroxytryptamine2 antagonist, up-regulates 5-hydroxytryptamine2 receptors in mouse brain".Mol Pharmacol.43 (1):84–89.doi:10.1016/S0026-895X(25)13451-2.PMID8423772.
^Rinaldi-Carmona M, Bouaboula M, Congy C, Oury-Donat F, Simiand J, Shire D, Casellas P, Soubrié P, Brelière JC, Le Fur G (June 1993). "Up-regulation of 5-HT2 receptors in the rat brain by repeated administration of SR 46349B, a selective 5-HT2 receptor antagonist".Eur J Pharmacol.246 (1):73–80.doi:10.1016/0922-4106(93)90012-x.PMID8354344.
^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.PMC3630942.PMID23616706.Eplivanserin (Ciltyri®, SR 46349B; trans, 4-[(3Z) 3-(2- dimethylamino-ethyl) oxyimino-3 (2-fluorophenyl) propen-1 -yl] phenol hemifumarate), was previously in development by Sanofi-aventis which coined the term "ASTAR" (Antagonist of Serotonin Two A Receptors), in an effort to educate the public regarding this new mechanism of action for sleep aids. Also originally designated as a 5-HT2 receptor antagonist,31 eplivanserin is even more selective than ritanserin for 5-HT2A over 5-HT2C 14 (Table 1). Eplivanserin was reviewed by the FDA as a potential treatment for patients with chronic insomnia, but the FDA requested additional information regarding benefitrisk (sanofi-aventis press release, September 16, 2009) and development of the drug has been discontinued (sanofi-aventis press release, December 21, 2009).
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