Safety, pharmacokinetics, and effects on cognitive function of multiple doses of GTS-21 in healthy, male volunteers

Neuropsychopharmacology. 2003 Mar;28(3):542-51. doi: 10.1038/sj.npp.1300028. Epub 2002 Jul 11.


This study was designed to determine the safety, tolerability, pharmacokinetics and effects on cognitive function of GTS-21 in healthy, male volunteers. A total of 18 subjects were randomized to GTS-21 (25, 75 and 150 mg) or placebo administered three times daily (first 4 days, once on Day 5) for three, 5-day sessions. GTS-21 was well tolerated up to doses of 450 mg/day, with no clinically significant safety findings. C(max) and the area under the plasma concentration of GTS-21 and the metabolite 4-OH-GTS-21 increased in a dose-related fashion; although considerable intersubject variability occurred, it decreased with continued dosing. GTS-21 showed statistically significant enhancement of three measures of cognitive function (attention, working memory, episodic secondary memory) compared to placebo. A relationship between exposure to GTS-21 and the magnitude of the cognitive response was apparent, with maximal effect approached for doses between 75 and 150 mg three times a day. These data indicate that GTS-21 may represent a novel treatment for dementia.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Area Under Curve
  • Benzylidene Compounds / administration & dosage
  • Benzylidene Compounds / adverse effects*
  • Benzylidene Compounds / chemistry
  • Benzylidene Compounds / pharmacokinetics*
  • Cognition / drug effects*
  • Cognition / physiology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Middle Aged
  • Pyridines / administration & dosage
  • Pyridines / adverse effects*
  • Pyridines / chemistry
  • Pyridines / pharmacokinetics*


  • Benzylidene Compounds
  • Pyridines
  • 3-(2,4-dimethoxybenzylidene)anabaseine