Vabicaserin

Vabicaserin

Vabicaserin
Systematic (IUPAC) name
(9aR,12aS)-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino[6,7,1-ij]quinoline
Clinical data
Legal status
  • Uncontrolled
Routes Oral
Identifiers
CAS number  YesY
ATC code None
PubChem
ChemSpider
UNII  YesY
Chemical data
Formula C15H21ClN2 
Mol. mass 264.79 g/mol
 YesY   

Vabicaserin (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. ^ "Enzyme Inhibition in Drug Discovery ... - Google Books". 
  3. ^ Prof John Kelly (2010). Principles of CNS Drug Development: From Test Tube to Patient. New York: Wiley.  
  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): 565–71.  
  5. ^ Tong Z, Chandrasekaran A, Demaio W, et al. (December 2009). "SPECIES DIFFERENCES IN THE FORMATION OF VABICASERIN CARBAMOYL GLUCURONIDE". Drug Metabolism and Disposition: the Biological Fate of Chemicals 38 (4): 581–590.  
  6. ^ a b "ECNP-2007 CIS". 
  7. ^ Stahl's essential psychopharmacology: neuroscientific basis and practical applications. Cambridge, UK: Cambridge University Press. 2008.  
  8. ^ Albert, JS (2012). Wood, MW, ed. Targets and Emerging Therapies for Schizophrenia. Hoboken, New Jersey: John Wiley & Sons, Inc.