STEREOSELECTIVE EFFECTS OF 2,3-BENZODIAZEPINES IN-VIVO - ELECTROPHYSIOLOGY AND NEUROPROTECTION STUDIES

The stereoselectivity and potency of 3N-substituted 2,3-benzodiazepine s were examined in vivo against excitation of spinal neurones induced by electrophoretic ejection of N-methyl-D-aspartate (NMDA), pha-amino- 3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and kainate in anaesth etised rats. AMPA receptor antagonist activity resided in the (-) isom ers, LY300164 and LY303070, which were effective given electrophoretic ally, intravenously (2.5-5 mg/kg) or orally (10 mg/kg). The same stere oselectivity was observed in neuroprotection studies. Thus, systemic a dministration of the (-) isomer, but not the (+) isomer, of these 2,3- benzodiazepines before or immediately after bilateral carotid artery o cclusion in the gerbil was neuroprotective. For example, 10 mg/kg of L Y300164 intraperitoneally or orally provided survival of up to 25% of hippocampal CA1 neurones. (C) 1997 Elsevier Science Ltd.