Vabicaserin Explained

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.^[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-HT_2C receptor full agonist (K_i = 3 nM; EC₅₀ = 8 nM; IA = 100% (relative to 5-HT)) and 5-HT_2B receptor antagonist (IC₅₀ = 29 nM).^{[4] [5] [6]} It is also a very weak antagonist at the 5-HT_2A receptor (IC₅₀ = 1,650 nM), though this action is not clinically significant.^[7] By activating 5-HT_2C 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.^{[8] [9]}

See also

• Lorcaserin
• WAY-163909

Notes and References

1. Web site: Search of: vabicaserin - List Results . ClinicalTrials.gov.
2. Book: Enzyme Inhibition in Drug Discovery ... . Google Books. 9780470538944. Lu C, Li AP . 26 January 2010. John Wiley & Sons .
3. Book: Kelly J . Principles of CNS Drug Development: From Test Tube to Patient . Wiley . New York . 2010 . 978-0-470-51979-0 .
4. Rosenzweig-Lipson S, Dunlop J, Marquis KL . 5-HT2C receptor agonists as an innovative approach for psychiatric disorders . Drug News & Perspectives . 20 . 9 . 565–571 . November 2007 . 18176661 . 10.1358/dnp.2007.20.9.1162244 .
5. Tong Z, Chandrasekaran A, DeMaio W, Jordan R, Li H, Moore R, Poola N, Burghart P, Hultin T, Scatina J . 6 . Species differences in the formation of vabicaserin carbamoyl glucuronide . Drug Metabolism and Disposition . 38 . 4 . 581–590 . April 2010 . 20032194 . 10.1124/dmd.109.028639 . 793693 .
6. Vabicaserin: effects of a novel 5HT2C agonist on medial prefrontal cortex neurotransmission, cognition and sensorimotor gating . 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 . 4 March 2012 . Rosenzweig-Lipson S, Beyer CE, Hughes Z, Lin Q, Zhang MY, Grauer S, Aschmies S, Comery T, Stack G, Marquis K . 6 . The Journal of the European College of Neuropsychopharmacology . 17 . Supplement 4 . S484 . 10.1016/S0924-977X(07)70740-X . 54245668 .
7. Rosenzweig-Lipson S, Dunlop J, Marquis KL . 5-HT2C receptor agonists as an innovative approach for psychiatric disorders . Drug News & Perspectives . 20 . 9 . 565–571 . November 2007 . 18176661 . 10.1358/dnp.2007.20.9.1162244 .
8. Book: Stahl SM . Stahl's essential psychopharmacology: neuroscientific basis and practical applications . Cambridge University Press . Cambridge, UK . 2008 . 978-0-521-85702-4 . 447 .
9. Book: Targets and Emerging Therapies for Schizophrenia . 3rd . John Wiley & Sons, Inc. Hoboken, New Jersey. 2012. 9781118309384. Albert JS. Wood MW .