title: The interaction of the neuroprotective compounds riluzole and phenobarbital with AMPA-type glutamate receptors: a patch-clamp study.
abstract: BACKGROUND
  Blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors is a promising pharmacological strategy in the treatment of neurodegenerative diseases. The aim of the study is to elucidate if there are direct interactions of riluzole and phenobarbital with AMPA-type receptor channels and to determinethe molecular pharmacological mechanisms.
  
  
  METHODS
  The patch-clamp technique was used combining an ultrafast solution exchange system to investigate the interaction of riluzole and phenobarbital with recombinant AMPA-type glutamate receptor channels (homomeric GluR2flipGQ or nondesensitizing GluR2L504Y).
  
  
  RESULTS
  A dose-dependent decrease in the relative peak current amplitude (rAmp) and the relative area-under-the-current curve (rAUC) were found after preincubation with 0.1 mmol/l or higher concentrations of riluzole. Furthermore, in coapplication experiments with GluR2L504Y, the application of 1 or 3 mmol/l riluzole showed a decrease in the current decay time constant, and a reopening current was observed at 3 mmol/l riluzole. Phenobarbital blocks AMPA receptor channels dose-dependently in the coapplication experiments, and reopening currents after removing glutamate and blocker were observed. A slight block effect after preincubation should indicate an additional competitive block effect.
  
  
  CONCLUSIONS
  Riluzole and phenobarbital modulate AMPA-type receptor channels separately, which could be both characterized as a combination of open-channel block and competitive-block mechanism.
authors.affiliation: Neurological Department of the Medical School Hannover and Center of Systems Neuroscience Hannover, Hannover, Germany. lingjingjin @ hotmail.com
authors.forename: Ling-Jing
authors.initials: LJ
authors.lastname: Jin
authors.forename: Friedrich
authors.initials: F
authors.lastname: Schlesinger
authors.forename: Yun-Ping
authors.initials: YP
authors.lastname: Song
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dengler
authors.forename: Klaus
authors.initials: K
authors.lastname: Krampfl
mesh_terms: D019540:Area Under Curve; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010634:Phenobarbital / Q000008:administration & dosage / Q000494:pharmacology*; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019782:Riluzole / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D018091:Receptors, AMPA; D019782:Riluzole; D010634:Phenobarbital