The AMPA modulator S 18986 improves declarative and working memory performances in aged mice

Behav Pharmacol. 2008 May;19(3):235-44. doi: 10.1097/FBP.0b013e3282feb0c1.


The aim of this study was to further characterize the memory-enhancing profile of S 18986 a positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors. S 18986 was studied in two mouse models of age-related memory deficits, using radial maze paradigms involving long-term/declarative memory and short-term/working memory. Aged mice exhibited severe deficits when compared with their younger counterparts in the two behavioural tests. S 18986 at the dose of 0.1 mg/kg selectively improved aged mouse performance in the test of long-term/declarative memory flexibility and exerted a beneficial effect on short-term retention of successive arm-visits in the short-term/working memory test. This study confirms the memory-enhancing properties of S 18986 and, in line with emerging data on multiple AMPA modulators, highlights the relevance of targeting AMPA receptors in the development of new memory enhancers.

MeSH terms

  • Aging
  • Animals
  • Behavior, Animal / drug effects
  • Benzothiadiazines / pharmacology*
  • Discrimination Learning / drug effects
  • Disease Models, Animal
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects*
  • Memory Disorders / drug therapy*
  • Memory, Short-Term / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Receptors, AMPA / drug effects*
  • Receptors, AMPA / metabolism


  • Benzothiadiazines
  • Receptors, AMPA
  • S18986-1