LY379268, a potent and selective Group II metabotropic glutamate receptor agonist, is neuroprotective in gerbil global, but not focal, cerebral ischaemia

Neurosci Lett. 1999 Oct 8;273(3):191-4. doi: 10.1016/s0304-3940(99)00663-1.


The neuroprotective effects of a selective Group II metabotropic glutamate receptor (mGluR) agonist, LY379268, have been evaluated against global and focal cerebral ischaemia. Loss of CA1 hippocampal neurones following 5 min bilateral occlusion of the carotid artery (BCAO) in the gerbil was almost completely prevented by LY379268 (10 mg/kg, i.p.) given 30 min post-occlusion (P < 0.001); 10 mg/kg 1 h after and 20 mg/kg 2 h after BCAO also produced significant neuroprotection (P < 0.05). Similarly the BCAO-induced increase in TUNEL positive cells at 5 days post-occlusion was reduced by LY379268. By contrast the size of the infarct following middle cerebral artery occlusion (MCAO) induced by endothelin-1 infusion in the rat was unaffected by either 10 or 20 mg/kg i.p. of LY379268. This contrast between the results from these two animal models with LY379268, agrees with previous data on a less potent but similarly selective mGluR2/3 agonist, LY354740. It further suggests that mGluR Group II agonists are likely to have more utility in global, than in focal, cerebral ischaemia.

MeSH terms

  • Amino Acids / therapeutic use*
  • Animals
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / pathology
  • Bridged Bicyclo Compounds / therapeutic use
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use*
  • Excitatory Amino Acid Agonists / therapeutic use
  • Gerbillinae
  • Hippocampus / blood supply
  • Hippocampus / drug effects*
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / pathology
  • Male
  • Neuroprotective Agents / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / agonists*
  • Stereoisomerism


  • Amino Acids
  • Bridged Bicyclo Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Excitatory Amino Acid Agonists
  • LY 379268
  • Neuroprotective Agents
  • Receptors, Metabotropic Glutamate
  • eglumetad