Vabicaserin
{{Short description|Chemical compound}}
{{cs1 config|name-list-style=vanc}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 451553573
| IUPAC_name = (9aR,12aS)-4,5,6,7,9,9a,10,11,12,12a-Decahydrocyclopenta[c][1,4]diazepino[6,7,1-ij]quinoline
| image = Vabicaserin.svg
| width = 150
| tradename =
| pregnancy_category =
| legal_status = Uncontrolled
| routes_of_administration = By mouth
| bioavailability =
| metabolism =
| elimination_half-life =
| excretion =
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 887258-95-9
| ATC_prefix = None
| ATC_suffix =
| PubChem = 11521822
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = WD9550HPNL
| C=15 | H=21 | Cl=1 | N=2
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 9696609
| smiles = C1C[C@H]2CN3CCNCC4=C3C(=CC=C4)[C@H]2C1
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C15H20N2/c1-3-11-9-16-7-8-17-10-12-4-2-5-13(12)14(6-1)15(11)17/h1,3,6,12-13,16H,2,4-5,7-10H2/t12-,13-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = NPTIPEQJIDTVKR-STQMWFEESA-N
}}
Vabicaserin (codenamed SCA-136) was a novel antipsychotic and anorectic under development by Wyeth.{{cite web | url = http://clinicaltrials.gov/ct2/results?term=vabicaserin | title = Search of: vabicaserin - List Results | work = ClinicalTrials.gov}} As of 2010 it is no longer in clinical trials for the treatment of psychosis.{{cite book | url = https://books.google.com/books?id=GS_98F19H74C&q=vabicaserin&pg=PA655 | title = Enzyme Inhibition in Drug Discovery ... | via = Google Books| isbn = 9780470538944| vauthors = Lu C, Li AP | date = 26 January 2010| publisher = John Wiley & Sons }} It was also under investigation as an antidepressant but this indication appears to have been dropped as well.{{cite book | vauthors = Kelly J | title = Principles of CNS Drug Development: From Test Tube to Patient | publisher = Wiley | location = New York | year = 2010 | isbn = 978-0-470-51979-0 | url = https://books.google.com/books?id=pfY3xcsu6EsC&q=vabicaserin%20antidepressant&pg=PA266}}
Vabicaserin acts as a selective 5-HT2C receptor full agonist (Ki = 3 nM; EC50 = 8 nM; IA = 100% (relative to 5-HT)) and 5-HT2B receptor antagonist (IC50 = 29 nM).{{cite journal | vauthors = Rosenzweig-Lipson S, Dunlop J, Marquis KL | title = 5-HT2C receptor agonists as an innovative approach for psychiatric disorders | journal = Drug News & Perspectives | volume = 20 | issue = 9 | pages = 565–571 | date = November 2007 | pmid = 18176661 | doi = 10.1358/dnp.2007.20.9.1162244 }}{{cite journal | vauthors = Tong Z, Chandrasekaran A, DeMaio W, Jordan R, Li H, Moore R, Poola N, Burghart P, Hultin T, Scatina J | display-authors = 6 | title = Species differences in the formation of vabicaserin carbamoyl glucuronide | journal = Drug Metabolism and Disposition | volume = 38 | issue = 4 | pages = 581–590 | date = April 2010 | pmid = 20032194 | doi = 10.1124/dmd.109.028639 | s2cid = 793693 }}{{cite journal | url = http://91.142.242.133/07ecnp/index.cfm?fuseaction=CIS2002&hoofdnav=Abstracts&content=abs.details&what=AUTHOR&searchtext=beyer&topicselected=*&selection=ABSTRACT&qryStartRowDetail=1 | archive-url = https://web.archive.org/web/20120304053452/http://91.142.242.133/07ecnp/index.cfm?fuseaction=CIS2002&hoofdnav=Abstracts&content=abs.details&what=AUTHOR&searchtext=beyer&topicselected=*&selection=ABSTRACT&qryStartRowDetail=1 | archive-date = 4 March 2012 | vauthors = Rosenzweig-Lipson S, Beyer CE, Hughes Z, Lin Q, Zhang MY, Grauer S, Aschmies S, Comery T, Stack G, Marquis K | display-authors = 6 | title = Vabicaserin: effects of a novel 5HT2C agonist on medial prefrontal cortex neurotransmission, cognition and sensorimotor gating | journal = The Journal of the European College of Neuropsychopharmacology | volume = 17 | issue = Supplement 4 | page = S484 | doi = 10.1016/S0924-977X(07)70740-X
| s2cid=54245668 }} It is also a very weak antagonist at the 5-HT2A receptor (IC50 = 1,650 nM), though this action is not clinically significant.{{cite journal | vauthors = Rosenzweig-Lipson S, Dunlop J, Marquis KL | title = 5-HT2C receptor agonists as an innovative approach for psychiatric disorders | journal = Drug News & Perspectives | volume = 20 | issue = 9 | pages = 565–571 | date = November 2007 | pmid = 18176661 | doi = 10.1358/dnp.2007.20.9.1162244 }} By activating 5-HT2C receptors, vabicaserin inhibits dopamine release in the mesolimbic pathway, likely underlying its efficacy in alleviating positive symptoms of schizophrenia, and increases acetylcholine and glutamate levels in the prefrontal cortex, suggesting benefits against cognitive symptoms as well.{{cite book | veditors = Stahl SM | title = Stahl's essential psychopharmacology: neuroscientific basis and practical applications | publisher = Cambridge University Press | location = Cambridge, UK | year = 2008 | isbn = 978-0-521-85702-4 | url = https://books.google.com/books?id=cWbYxSfKN3cC&q=vabicaserin&pg=PA447 | page = 447 }}{{cite book|title=Targets and Emerging Therapies for Schizophrenia | edition = 3rd |publisher=John Wiley & Sons, Inc|location=Hoboken, New Jersey|date=2012|isbn=9781118309384| vauthors = Albert JS| veditors = Wood MW }}