Vabicaserin

Chemical compound
  • None
Legal statusLegal status
  • In general: uncontrolled
Identifiers
  • (9aR,12aS)-4,5,6,7,9,9a,10,11,12,12a-Decahydrocyclopenta[c][1,4]diazepino[6,7,1-ij]quinoline
CAS Number
  • 887258-95-9 checkY
PubChem CID
  • 11521822
ChemSpider
  • 9696609 ☒N
UNII
  • WD9550HPNL
CompTox Dashboard (EPA)
  • DTXSID80977680 Edit this at Wikidata
Chemical and physical dataFormulaC15H21ClN2Molar mass264.80 g·mol−13D model (JSmol)
  • Interactive image
  • C1C[C@H]2CN3CCNCC4=C3C(=CC=C4)[C@H]2C1
InChI
  • InChI=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 ☒N
  • Key:NPTIPEQJIDTVKR-STQMWFEESA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Vabicaserin (codenamed SCA-136) was a novel antipsychotic and anorectic under development by Wyeth.[1] As of 2010 it is no longer in clinical trials for the treatment of psychosis.[1][2] It was also under investigation as an antidepressant but this indication appears to have been dropped as well.[3]

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).[4][5][6] It is also a very weak antagonist at the 5-HT2A receptor (IC50 = 1,650 nM), though this action is not clinically significant.[4] 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.[6][7][8]

See also

References

  1. ^ a b "Search of: vabicaserin - List Results". ClinicalTrials.gov.
  2. ^ Lu C, Li AP (26 January 2010). Enzyme Inhibition in Drug Discovery ... John Wiley & Sons. ISBN 9780470538944 – via Google Books.
  3. ^ Kelly J (2010). Principles of CNS Drug Development: From Test Tube to Patient. New York: Wiley. ISBN 978-0-470-51979-0.
  4. ^ a b Rosenzweig-Lipson S, Dunlop J, Marquis KL (November 2007). "5-HT2C receptor agonists as an innovative approach for psychiatric disorders". Drug News & Perspectives. 20 (9): 565–571. doi:10.1358/dnp.2007.20.9.1162244. PMID 18176661.
  5. ^ Tong Z, Chandrasekaran A, DeMaio W, Jordan R, Li H, Moore R, et al. (April 2010). "Species differences in the formation of vabicaserin carbamoyl glucuronide". Drug Metabolism and Disposition. 38 (4): 581–590. doi:10.1124/dmd.109.028639. PMID 20032194. S2CID 793693.
  6. ^ a b Rosenzweig-Lipson S, Beyer CE, Hughes Z, Lin Q, Zhang MY, Grauer S, et al. "Vabicaserin: effects of a novel 5HT2C agonist on medial prefrontal cortex neurotransmission, cognition and sensorimotor gating". The Journal of the European College of Neuropsychopharmacology. 17 (Supplement 4): S484. doi:10.1016/S0924-977X(07)70740-X. S2CID 54245668. Archived from the original on 4 March 2012.
  7. ^ Stahl SM, ed. (2008). Stahl's essential psychopharmacology: neuroscientific basis and practical applications. Cambridge, UK: Cambridge University Press. p. 447. ISBN 978-0-521-85702-4.
  8. ^ Albert JS (2012). Wood MW (ed.). Targets and Emerging Therapies for Schizophrenia (3rd ed.). Hoboken, New Jersey: John Wiley & Sons, Inc. ISBN 9781118309384.
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Stimulants
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5-HT1
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  • See also: Receptor/signaling modulators
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