A randomized exploratory trial of an α-7 nicotinic receptor agonist (TC-5619) for cognitive enhancement in schizophrenia

Neuropsychopharmacology. 2013 May;38(6):968-75. doi: 10.1038/npp.2012.259. Epub 2012 Dec 18.


This exploratory trial was conducted to test the effects of an alpha7 nicotinic receptor partial agonist, TC-5619, on cognitive dysfunction and negative symptoms in subjects with schizophrenia. In the United States and India, 185 outpatients (18-60 years; male 69%; 46% tobacco users) with schizophrenia treated with quetiapine or risperidone monotherapy were randomized to 12 weeks of placebo (n=91) or TC-5619 (n=94; orally once daily 1 mg day 1 to week 4, 5 mg week 4 to 8, and 25 mg week 8 to 12). The primary efficacy outcome measure was the Groton Maze Learning Task (GMLT; executive function) of the CogState Schizophrenia Battery (CSB). Secondary outcome measures included: CSB composite score; Scale for Assessment of Negative Symptoms (SANS); Clinical Global Impression-Global Improvement (CGI-I); CGI-severity (CGI-S); and Subject Global Impression-Cognition. GMLT statistically favored TC-5619 (P=0.036) in this exploratory trial. SANS also statistically favored TC-5619 (P=0.030). No other secondary outcome measure demonstrated a drug effect in the total population; there was a statistically significant drug effect on working memory in tobacco users. The results were typically stronger in favor of TC-5619 in tobacco users and occasionally better in the United States than in India. TC-5619 was generally well tolerated with no clinically noteworthy safety findings. These results support the potential benefits of TC-5619 and alpha7 nicotinic receptor partial agonists for cognitive dysfunction and negative symptoms in schizophrenia.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / therapeutic use
  • Benzofurans / therapeutic use*
  • Female
  • Humans
  • India / epidemiology
  • Male
  • Middle Aged
  • Nicotinic Agonists / therapeutic use*
  • Nootropic Agents / therapeutic use*
  • Quinuclidines / therapeutic use*
  • Schizophrenia / drug therapy*
  • Schizophrenia / epidemiology
  • Schizophrenic Psychology*
  • United States / epidemiology
  • Young Adult
  • alpha7 Nicotinic Acetylcholine Receptor / physiology*


  • Antipsychotic Agents
  • Benzofurans
  • N-(2-(pyridin-3-ylmethyl)-1-azabicyclo(2.2.2)oct-3-yl)-1-benzofuran-2-carboxamide
  • Nicotinic Agonists
  • Nootropic Agents
  • Quinuclidines
  • alpha7 Nicotinic Acetylcholine Receptor