Protective effect of gabapentin on N-methyl-D-aspartate-induced excitotoxicity in rat hippocampal CA1 neurons

J Pharmacol Sci. 2009 Jan;109(1):144-7. doi: 10.1254/jphs.08067sc.

Abstract

Gabapentin was developed as an anticonvulsant, but has also been used to alleviate hyperalgesia in neuropathic pain. In this study, the protective effect of gabapentin against N-methyl-D-aspartate (NMDA)-induced excitotoxicity in rat hippocampal CA1 neurons was investigated. Pre-treatment with gabapentin reduced the degree of neuronal damage induced by NMDA exposure in cultured hippocampal slices. Patch-clamp studies revealed that gabapentin significantly inhibited the NMDA receptor-activated ion current in dissociated hippocampal CA1 neurons, resulting in suppression of glutamate-induced neuronal injury. These results show that gabapentin may exert protective effects against glutamate-induced neuronal injury at least in part by inhibiting the NMDA receptor-activated ion current.

MeSH terms

  • Amines / pharmacology*
  • Animals
  • Animals, Newborn
  • Anticonvulsants / pharmacology
  • Cyclohexanecarboxylic Acids / pharmacology*
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Agonists / toxicity
  • Gabapentin
  • Hippocampus / cytology
  • Ion Channels / physiology
  • Membrane Potentials / drug effects
  • N-Methylaspartate / toxicity*
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / physiology
  • Neuroprotective Agents / pharmacology*
  • Patch-Clamp Techniques / methods
  • Pyramidal Cells / cytology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / physiology
  • gamma-Aminobutyric Acid / pharmacology*

Substances

  • Amines
  • Anticonvulsants
  • Cyclohexanecarboxylic Acids
  • Excitatory Amino Acid Agonists
  • Ion Channels
  • Neuroprotective Agents
  • Receptors, N-Methyl-D-Aspartate
  • gamma-Aminobutyric Acid
  • N-Methylaspartate
  • Gabapentin