Encenicline

Encenicline (INN,[1] USAN, code names EVP-6124, MT-4666) is a selective partial agonist of the α7 nicotinic receptor. It was in phase III clinical trials for the treatment of cognitive impairment in schizophrenia,[2][3] unfortunately it failed to meet the study endpoints in 2016.[4]

Encenicline
Clinical data
ATC code
  • None
Identifiers
IUPAC name
  • N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-chloro-1-benzothiophene-2-carboxamide
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC16H17ClN2OS
Molar mass320.83 g·mol−1
3D model (JSmol)
SMILES
  • c1cc2cc(sc2c(c1)Cl)C(=O)N[C@H]3CN4CCC3CC4
InChI
  • InChI=1S/C16H17ClN2OS/c17-12-3-1-2-11-8-14(21-15(11)12)16(20)18-13-9-19-6-4-10(13)5-7-19/h1-3,8,10,13H,4-7,9H2,(H,18,20)/t13-/m0/s1
  • Key:SSRDSYXGYPJKRR-ZDUSSCGKSA-N

FORUM Pharmaceuticals, who currently is subjecting the drug to the FDA approval process, had all studies suspended until further notice in fall of 2015 due to rare, but serious gastrointestinal problems occurring in patients participating in the drug trial, potentially being a consequence of taking the drug. The trials were scheduled to be run until January 2017, but as of December 2016, they appear to still be on hold. There is speculation by FORUM Pharmaceuticals that this may be due to either the increased daily dose given in the phase III trial compared to earlier trials that showed promise. In previous trials, the highest dose given was 2 mg/day, with the most positive of effects having been realized in patients taking the largest dose (2 mg/day). In the phase III trial, all patients were treated with 3 mg/day doses of the drug. FORUM also speculates that the increase of gastrointestinal problems occurring in the phase III trial could be due to the increased demographic risk that elderly (the average age in the study was 75) and those with Alzheimer's disease have in regard to gastrointestinal issues, citing another study they conducted with a younger demographic (in which the average age was 35–40) for the treatment of schizophrenia of 1,500 individuals in which there were zero complains of gastrointestinal problems.[5]

See also

References
  1. "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 73" (PDF). World Health Organization. p. 84. Retrieved 3 January 2017.
  2. Melville NA. "Novel Drug Targets 'Huge Unmet Need' in Schizophrenia". Medscape. Retrieved 13 April 2015.
  3. Barbier AJ, Hilhorst M, Van Vliet A, Snyder P, Palfreyman MG, Gawryl M, et al. (February 2015). "Pharmacodynamics, pharmacokinetics, safety, and tolerability of encenicline, a selective α7 nicotinic receptor partial agonist, in single ascending-dose and bioavailability studies". Clinical Therapeutics. 37 (2): 311–24. doi:10.1016/j.clinthera.2014.09.013. PMID 25438724.
  4. "Encenicline Misses Endpoints in Two Phase 3 Schizophrenia Trials | ALZFORUM". www.alzforum.org. Retrieved 2021-05-01.
  5. "Rare but Severe Side Effects Sideline Some Phase 3 Encenicline Trials". Alzforum. 16 September 2015.


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