Stereoselective effects-of 2,3-benzodiazepines in vivo: electrophysiology and neuroprotection studies

Neuropharmacology. 1996;35(12):1681-8. doi: 10.1016/s0028-3908(96)00155-4.


The stereoselectivity and potency of 3N-substituted 2,3-benzodiazepines were examined in vivo against excitation of spinal neurones induced by electrophoretic ejection of N-methyl-D-aspartate (NMDA), alpha-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.

MeSH terms

  • Animals
  • Benzodiazepines / pharmacology*
  • Electrophysiology
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Female
  • Ischemic Attack, Transient / physiopathology*
  • Isomerism
  • N-Methylaspartate / pharmacology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Rats, Wistar
  • Spinal Cord / physiology*
  • Spinal Cord / physiopathology
  • Structure-Activity Relationship
  • Time Factors
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology*


  • Excitatory Amino Acid Antagonists
  • Neuroprotective Agents
  • Benzodiazepines
  • N-Methylaspartate
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid