| Autor: |
LODGE, DAVID, BOND, ANN, O'NEILL, MICHAEL J, HICKS, CAROLINE A, JONES, MARTYN G |
| Zdroj: |
Neuropharmacology; December 1996, Vol. 35 Issue: 12 p1681-1688, 8p |
| Abstrakt: |
The stereoselectivity and potency of 3N-substituted 2,3-benzodiazepines were examined in vivoagainst excitation of spinal neurons induced by electrophoretic ejection of N-methyl-d-aspartate (NMDA), α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and kainate in anaesthetised rats. AMPA receptor antagonist activity resided in the (−) isomers, LY300164 and LY303070, which were effective given electrophoretically, intravenously (2.5–5 mg/kg) or orally (10 mg/kg). The same stereoselectivity was observed in neuroprotection studies. Thus, systemic administration of the (−) isomer, but not the (+) isomer, of these 2,3-benzodiazepines before or immediately after bilateral carotid artery occlusion in the gerbil was neuroprotective. For example, 10 mg/kg of LY300164 intraperitoneally or orally provided survival of up to 25% of hippocampal CA1 neurones. © 1997 Elsevier Science Ltd. All rights reserved. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
Full Text from ScienceDirect