Memory restoring and neuroprotective effects of the proline-containing dipeptide, GVS-111, in a photochemical stroke model

Behav Pharmacol. 1999 Sep;10(5):549-53. doi: 10.1097/00008877-199909000-00013.

Abstract

Local thrombosis of the frontal cortex (Fr1 and Fr3 fields), caused by combination of the intravenous photosensitive dye Rose Bengal administration with focused high-intensity illumination of the frontal bone, was shown to provoke a pronounced deficit in step-through passive avoidance performance in rats without concomitant motor disturbances. N-Phenylacetyl-L-prolylglycine ethyl ester (GVS-111) administered intravenously at a dose of 0.5 mg/kg/day, for the first time 1 h after ischaemic lesion and then for 9 post-operative days, with the last administration 15 min before testing, attenuated the deficit. This treatment significantly diminished the volume of the infarcted area. Thus, post-ischaemic injection of GVS-111 demonstrated both cognition-restoring and neuroprotective properties. The cognition-restoring effect is probably based on an increase in neocortical and hippocampal neuronal plasticity. Neuroprotective effects of GVS-111 combine antioxidant activity with the ability to attenuate glutamate-provoked neurotoxicity and block voltage-gated ionic channels, i.e. the compound mitigates the main metabolic shifts involved in pathogenesis of brain ischaemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning / drug effects
  • Brain Mapping
  • Dipeptides / pharmacology*
  • Dose-Response Relationship, Drug
  • Frontal Lobe / pathology
  • Frontal Lobe / physiopathology
  • Intracranial Embolism / pathology
  • Intracranial Embolism / physiopathology*
  • Male
  • Mental Recall / drug effects*
  • Mental Recall / physiology
  • Neuronal Plasticity / drug effects
  • Nootropic Agents / pharmacology*
  • Rats
  • Rats, Wistar

Substances

  • Dipeptides
  • Nootropic Agents
  • ethyl phenylacetyl-Pro-Gly