Pruvanserin

Pruvanserin (INNTooltip International Nonproprietary Name; USANTooltip United States Adopted Name; developmental code names EMD-281,014, LY-2422347) is a selective serotonin 5-HT_2A receptor antagonist which was under development by Eli Lilly and Company for the treatment of insomnia.^[1]^[3]^[4] It was in phase II clinical trials in 2008 but appears to have been discontinued as it is no longer in the company's development pipeline.^[5]^[6]

Other namesEMD-281,014; EMD-281014; LY-2422347; LY2422347; LSN2411347; LSN-2411347

Routes of
administrationOral^[1]

Drug classSerotonin 5-HT_2A receptor antagonist

ATC code

None

Quick facts Clinical data, Other names ...

Pruvanserin
Clinical data

Other names	EMD-281,014; EMD-281014; LY-2422347; LY2422347; LSN2411347; LSN-2411347
Routes of administration	Oral^[1]
Drug class	Serotonin 5-HT_2A receptor antagonist
ATC code	None
Legal status
Legal status	In general: uncontrolled
Pharmacokinetic data
Onset of action	T_maxTooltip Time to peak levels: 2–3 hours (range 2–6 hours)^[2]
Elimination half-life	8.6–9.5 hours (range 3.9–12.4 hours)^[2]
Identifiers
IUPAC name 7-[4-[2-(4-fluorophenyl)ethyl]piperazine-1-carbonyl]-1H-indole-3-carbonitrile
CAS Number	443144-26-1 443144-27-2 (hydrochloride)
PubChem CID	6433122
DrugBank	DB13094
ChemSpider	4938310
UNII	UL09X1D9EM
KEGG	D06632
ChEBI	CHEBI:177485
ChEMBL	ChEMBL1215661
CompTox Dashboard (EPA)	DTXSID40196133
Chemical and physical data
Formula	C₂₂H₂₁FN₄O
Molar mass	376.435 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES C1CN(CCN1CCC2=CC=C(C=C2)F)C(=O)C3=CC=CC4=C3NC=C4C#N
InChI InChI=1S/C22H21FN4O/c23-18-6-4-16(5-7-18)8-9-26-10-12-27(13-11-26)22(28)20-3-1-2-19-17(14-24)15-25-21(19)20/h1-7,15,25H,8-13H2 Key:AQRLDDAFYYAIJP-UHFFFAOYSA-N

Pharmacology

Pharmacodynamics

Pruvanserin acts as a selective serotonin 5-HT_2A receptor antagonist. In addition to its sleep-improving properties,^[7]^[8] pruvanserin has also been shown to have antidepressant, anxiolytic, and working memory-enhancing effects in animal studies.^[9]^[10]^[11]

Pharmacodynamics

The time to peak levels of pruvanserin is 2 to 3 hours, with a range of 2 to 6 hours.^[2] The mean elimination half-life of pruvanserin is 8.6 to 9.5 hours, with a range of 3.9 to 12.4 hours.^[2] However, its brain serotonin 5-HT_2A receptor occupancy lasts much longer, with a half-life of approximately 24 hours.^[2]

References

[1]
"Pruvanserin". AdisInsight. 19 August 2014. Retrieved 16 January 2026.
[2]
Mamo D, Sedman E, Tillner J, Sellers EM, Romach MK, Kapur S (September 2004). "EMD 281014, a specific and potent 5HT2 antagonist in humans: a dose-finding PET study". Psychopharmacology (Berl). 175 (3): 382–388. doi:10.1007/s00213-004-1817-7. PMID 15007535.
[3]
Bartoszyk GD, van Amsterdam C, Böttcher H, Seyfried CA (July 2003). "EMD 281014, a new selective serotonin 5-HT2A receptor antagonist". European Journal of Pharmacology. 473 (2–3): 229–30. doi:10.1016/S0014-2999(03)01992-7. PMID 12892843.
[4]
Teegarden 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. PMID 18673166.
[5]
"Efficacy Study of LY2422347 to Treat Insomnia - Full Text View - ClinicalTrials.gov". 24 January 2007.
[6]
"Eli Lilly and Company » Research Pipeline".
[7]
Monti JM, Jantos H (September 2006). "Effects of activation and blockade of 5-HT2A/2C receptors in the dorsal raphe nucleus on sleep and waking in the rat". Progress in Neuro-psychopharmacology & Biological Psychiatry. 30 (7): 1189–95. doi:10.1016/j.pnpbp.2006.02.013. PMID 16713054. S2CID 12837755.
[8]
Monti JM, Jantos H (December 2006). "Effects of the serotonin 5-HT2A/2C receptor agonist DOI and of the selective 5-HT2A or 5-HT2C receptor antagonists EMD 281014 and SB-243213, respectively, on sleep and waking in the rat". European Journal of Pharmacology. 553 (1–3): 163–70. doi:10.1016/j.ejphar.2006.09.027. PMID 17059817.
[9]
Patel JG, Bartoszyk GD, Edwards E, Ashby CR (April 2004). "The highly selective 5-hydroxytryptamine (5-HT)2A receptor antagonist, EMD 281014, significantly increases swimming and decreases immobility in male congenital learned helpless rats in the forced swim test". Synapse. 52 (1): 73–5. doi:10.1002/syn.10308. PMID 14755634. S2CID 21941333.
[10]
Adamec R, Creamer K, Bartoszyk GD, Burton P (November 2004). "Prophylactic and therapeutic effects of acute systemic injections of EMD 281014, a selective serotonin 2A receptor antagonist on anxiety induced by predator stress in rats". European Journal of Pharmacology. 504 (1–2): 79–96. doi:10.1016/j.ejphar.2004.09.017. PMID 15507224.
[11]
Terry AV, Buccafusco JJ, Bartoszyk GD (June 2005). "Selective serotonin 5-HT2A receptor antagonist EMD 281014 improves delayed matching performance in young and aged rhesus monkeys". Psychopharmacology. 179 (4): 725–32. doi:10.1007/s00213-004-2114-1. PMID 15619109. S2CID 30366683.

Pharmacology

Pharmacodynamics

Pharmacodynamics

See also

References

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