Gabapentin activates presynaptic GABAB heteroreceptors in rat cortical slices

Eur J Pharmacol. 2004 Jul 14;495(2-3):137-43. doi: 10.1016/j.ejphar.2004.05.029.

Abstract

In electrically stimulated rat neocortical brain slices preloaded with [3H]gamma-aminobutyric acid (GABA) or [3H]glutamic acid, the pharmacological actions of 1-(aminomethyl)-cyclohexaneacetic acid (gabapentin, Gp) were compared with the GABAB receptor agonists baclofen (Bac) and (3-amino-2-(S)-hydroxypropyl)-methylphosphinic acid (CGP 44532). Gabapentin, baclofen and CGP 44532 all reduced the electrically stimulated release of [3H]glutamic acid (IC50=20 microM, 0.8 microM and 2 microM, respectively). These effects were sensitive to the GABAB receptor antagonists (+)-(S)-5,5 dimethylmorpholinyl-2-acetic acid (Sch 50911) or N-3-[[1-(S)-(3,4-dichlorophenyl)ethyl]amino]-2-(S)-hydroxypropyl-P-(cyclo-hexylmethyl)-phosphinic acid (CGP 54626). By contrast, gabapentin was without effect on the release of [3H]GABA, whilst baclofen (IC50=8 microM) and CGP 44532 (IC50=1 microM) inhibited [3H]GABA release. It is concluded that gabapentin selectively activates presynaptic GABAB heteroreceptors, but not GABAB autoreceptors, and may be a useful ligand to discriminate between presynaptic GABAB receptor subtypes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / pharmacology*
  • Animals
  • Baclofen / pharmacology
  • Cyclohexanecarboxylic Acids / pharmacology*
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology
  • GABA Agonists / pharmacology
  • Gabapentin
  • Glutamic Acid / metabolism
  • In Vitro Techniques
  • Male
  • Morpholines / pharmacology
  • Neocortex / drug effects*
  • Neocortex / metabolism
  • Organophosphorus Compounds / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-B / metabolism*
  • Receptors, Presynaptic / metabolism*
  • Tritium / metabolism
  • gamma-Aminobutyric Acid / metabolism
  • gamma-Aminobutyric Acid / pharmacology*

Substances

  • (+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid
  • Amines
  • Cyclohexanecarboxylic Acids
  • Excitatory Amino Acid Antagonists
  • GABA Agonists
  • Morpholines
  • Organophosphorus Compounds
  • Receptors, GABA-B
  • Receptors, Presynaptic
  • Tritium
  • CGP 54626
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Baclofen