Lack of neuroprotective effect of some sigma ligands in a model of focal cerebral ischemia in the mouse.
The potential neuroprotective effect of seven sigma 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) antagonists. When given after the induction of cerebral ischemia, the NMDA receptor antagonists dizocilpine and CGS 19755 and the mixed NMDA antagonist/sigma ligand eliprodil (SL 82.0715) afforded very substantial protection against cortical 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 sigma 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.
Poignet
H
H
Synthelabo Recherche, LERS, Biology Department, Bagneux, France.
Nowicki
J P
JP
Scatton
B
B
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology; D007546:Isoquinolines / Q000378:metabolism; D008024:Ligands; D008297:Male; D051379:Mice; D010880:Piperidines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D017480:Receptors, sigma / Q000378:metabolism*
D006146:Guanidines; D007546:Isoquinolines; D008024:Ligands; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D017480:Receptors, sigma; C037850:PK 11195; C058083:eliprodil