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

Abstract

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.

• Authors: H Poignet, J P Nowicki, B Scatton
• Journal: Brain research (Brain Res) Vol. 596 Issue 1-2 Pg. 320-4 (Nov 20 1992) ISSN: 0006-8993 [Print] Netherlands
• PMID: 1467996 (Publication Type: Journal Article)

Chemical References

• Guanidines
• Isoquinolines
• Ligands
• Piperidines
• Receptors, N-Methyl-D-Aspartate
• Receptors, sigma
• PK 11195
• eliprodil

Topics

• Animals
• Brain Ischemia (pathology)
• Cerebral Cortex (drug effects, metabolism, pathology)
• Dose-Response Relationship, Drug
• Guanidines (pharmacology)
• Isoquinolines (metabolism)
• Ligands
• Male
• Mice
• Piperidines (pharmacology)
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)
• Receptors, sigma (metabolism)