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

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.

• Authors: A W O'Connell, G B Fox, C Kjøller, H C Gallagher, K J Murphy, J Kelly, C M Regan
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 424 Issue 1 Pg. 37-44 (Jul 13 2001) ISSN: 0014-2999 [Print] Netherlands
• PMID: 11470258 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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