title: Antinociception and (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid antagonism by gabapentin in the rat spinal cord in vivo.
abstract: Gabapentin, a novel anticonvulsant and analgesic with an unknown mechanism of action, was tested on spinal dorsal horn neurone activity evoked by iontophoretically applied N-methyl-D-aspartic acid (NMDA) and (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and on nociceptive responses of single motor units (SMU) in anaesthetised rats. Gabapentin (10-215 mg/kg, i.v.) dose-dependently and selectively inhibited AMPA-evoked neuronal responses (ED50 106+/-24 mg/kg); no effect on NMDA-evoked activity was observed. In the same dose-range, gabapentin (10-215 mg/ kg, i.v.) dose-dependently reduced SMU responses to noxious electrical and mechanical stimulation. We conclude that gabapentin acts as an AMPA antagonist in the rat spinal cord, and that this mechanism is likely to substantially contribute to the antinociceptive effect of the drug.
authors.affiliation: Department of Pharmacology, Grünenthal GmbH Research and Development, Aachen, Germany. boris.chizh@grunenthal.com
authors.forename: B A
authors.initials: BA
authors.lastname: Chizh
authors.forename: M
authors.initials: M
authors.lastname: Scheede
authors.forename: H
authors.initials: H
authors.lastname: Schlütz
mesh_terms: D000085:Acetates / Q000008:administration & dosage / Q000494:pharmacology*; D000588:Amines; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003509:Cyclohexanecarboxylic Acids; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D000077206:Gabapentin; D007278:Injections, Spinal; D007478:Iontophoresis; D008297:Male; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects; D005680:gamma-Aminobutyric Acid
chemical_list: D000085:Acetates; D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D001640:Bicuculline