Lack of neuroprotective effect of some σ ligands in a model of focal cerebral ischemia in the mouse

Abstract The potential neuroprotective effect of seven σ ligands has been evaluated in a mouse model of focal cerebral ischemia (induced by coagulation of the left middle cerebral artery) and compared to that of known N- methyl - d - aspartate (NMDA) antagonist. When given after the induction of cerebral ischemia, the NMDA receptor antagonist dizocilpine and CGS 19755 and the mixed NMDA antagonist/ σ ligand eliprodil (SL 82.0715) afforded very substantial protection against cortial infarction (92, 44 and 72%, at the doses of 1, 10 and 10 mg/kg, i.p., for dizocilpine, CGS 19755 and eliprodil, respectively). In contrast, none of the σ ligands investigated - DTG, DMTG, GBR 12909, (+)- and (−)-3-PPP (up to 10 mg/kg), BMY 14802 (up to 30 mg/kg), except haloperidol at a high dose (3 mg/kg) - had neuroprotective effects.