title: LY379268, a potent and selective Group II metabotropic glutamate receptor agonist, is neuroprotective in gerbil global, but not focal, cerebral ischaemia.
abstract: 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.
authors.affiliation: Eli Lilly & Co., Ltd., Lilly Research Centre, Erl Wood Manor, Surrey, UK.
authors.forename: A
authors.initials: A
authors.lastname: Bond
authors.forename: N
authors.initials: N
authors.lastname: Ragumoorthy
authors.forename: J A
authors.initials: JA
authors.lastname: Monn
authors.forename: C A
authors.initials: CA
authors.lastname: Hicks
authors.forename: M A
authors.initials: MA
authors.lastname: Ward
authors.forename: D
authors.initials: D
authors.lastname: Lodge
authors.forename: M J
authors.initials: MJ
authors.lastname: O'Neill
mesh_terms: D000596:Amino Acids / Q000627:therapeutic use*; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D001643:Bridged Bicyclo Compounds / Q000627:therapeutic use; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000627:therapeutic use*; D018690:Excitatory Amino Acid Agonists / Q000627:therapeutic use; D005849:Gerbillinae; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013237:Stereoisomerism
chemical_list: D000596:Amino Acids; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018690:Excitatory Amino Acid Agonists; C118218:LY 379268; D018696:Neuroprotective Agents; D018094:Receptors, Metabotropic Glutamate; C104753:eglumetad