Anti-ischemic and cognition-enhancing properties of NNC-711, a gamma-aminobutyric acid reuptake inhibitor

Eur J Pharmacol. 2001 Jul 13;424(1):37-44. doi: 10.1016/s0014-2999(01)01116-5.

Abstract

NNC-711 [1-(2-((diphenylmethylene)amino)oxy)ethyl)-1,2,4,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride], a gamma-aminobutyric acid (GABA) reuptake inhibitor with anticonvulsant activity, was investigated with respect to its cognition-enhancing and neuroprotective potency. In the rat, administration of NNC-711 immediately prior to training prevented amnesia for a passive avoidance task induced by the acetylcholine receptor antagonist scopolamine. NNC-711 was also effective in protecting against ischemia-induced death of CA1 pyramidal neurons in a model of bilateral common carotid artery occlusion in the gerbil. In addition to a neuroprotective activity, NNC-711 exhibited significant cognition-enhancing actions. Daily administration of NNC-711, immediately prior to a spatial learning task, significantly reduced escape latencies in the water maze paradigm in both mature (postnatal day 80) and aged (28 months) rats. All of the above actions exhibited a bell-shaped response with an optimal dose of 0.5-1.0 mg/kg. These investigations with NNC-711 and previous clinical observations on the structurally related anticonvulsant tiagabine confirm the potential of GABA reuptake inhibitors as anti-amnesia and cognition-enhancing agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amnesia / chemically induced
  • Amnesia / prevention & control
  • Animals
  • Avoidance Learning / drug effects
  • Cell Survival / drug effects
  • Cognition / drug effects*
  • Cognition / physiology
  • Dose-Response Relationship, Drug
  • GABA Antagonists / pharmacology*
  • Gerbillinae
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Ischemic Attack, Transient / physiopathology
  • Ischemic Attack, Transient / prevention & control*
  • Male
  • Maze Learning / drug effects
  • Neuroprotective Agents / pharmacology
  • Nipecotic Acids / pharmacology*
  • Oximes / pharmacology*
  • Rats
  • Rats, Wistar
  • Scopolamine / administration & dosage

Substances

  • GABA Antagonists
  • Neuroprotective Agents
  • Nipecotic Acids
  • Oximes
  • NNC 711
  • Scopolamine