Vabicaserin: Difference between revisions

{{Short description|Chemical compound}}

{{cs1 config|name-list-style=vanc}}

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 451553573

| IUPAC_name = (9a''R'',12a''S'')-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 =

| routes_of_administration = [[Oral 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

| 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]].<ref name="urlSearch of: vabicaserin - List Results - ClinicalTrials.gov">{{cite web | url = http://clinicaltrials.gov/ct2/results?term=vabicaserin | title = Search of: vabicaserin - List Results | work = ClinicalTrials.gov}}</ref> As of 2010 it is no longer in [[clinical trial]]s for the treatment of [[psychosis]].<ref name="urlSearch of: vabicaserin - List Results - ClinicalTrials.gov" /><ref name="urlEnzyme Inhibition in Drug Discovery ... - Google Books">{{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 }}</ref> It was also under investigation as an [[antidepressant]] but this indication appears to have been dropped as well.<ref name="isbn0-470-51979-7">{{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}}</ref>

Vabicaserin acts as a [[binding selectivity|selective]] [[5-HT2C receptor|5-HT_2C receptor]] [[full agonist]] (K_i = 3 nM; EC₅₀ = 8 nM; IA = 100% (relative to [[serotonin|5-HT]])) and [[5-HT2B receptor|5-HT_2B receptor]] [[receptor antagonist|antagonist]] (IC₅₀ = 29 nM).<ref name="pmid18176661">{{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 }}</ref><ref name="pmid20032194">{{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 }}</ref><ref name="urlECNP-2007 CIS">{{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 }}</ref> It is also a very weak antagonist at the [[5-HT2A receptor|5-HT_2A receptor]] (IC₅₀ = 1,650 nM), though this action is not clinically significant.<ref name="pmid18176661">{{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 }}</ref> By activating 5-HT_2C receptors, vabicaserin inhibits [[dopamine]] release in the [[mesolimbic pathway]], likely underlying its efficacy in alleviating [[Schizophrenia#Positive and negative symptoms|positive symptom]]s of [[schizophrenia]], and increases [[acetylcholine]] and [[glutamate]] levels in the [[prefrontal cortex]], suggesting benefits against [[Schizophrenia#Positive and negative symptoms|cognitive symptom]]s as well.<ref name="urlECNP-2007 CIS" /><ref name="isbn0-521-85702-3">{{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 }}</ref><ref>{{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 }}</ref>

* [[WAY-163909]]

{{reflist|30em}}

[[Category:Pyridobenzodiazepines]]

[[Category:Quinolines]]

[[Category:Cyclopentanes]]