GYKI 52466 has positive modulatory effects on AMPA receptors.
The 2,3-benzodiazepine derivative GYKI 52466 has been well characterized as a negative modulator of AMPA-type glutamate receptors. The present study re-examined the effects of GYKI 52466 on AMPA receptor-mediated currents in patches excised from pyramidal neurons in the hippocampal CA1 field and found that this drug has positive modulatory effects in addition to its receptor blocking action. A low concentration of GYKI 52466 (10 microM) reliably increased the steady-state current by about three-fold, while the peak current was reduced by 30% only. Higher drug concentrations produced parallel reductions in both the steady-state and peak currents. The increase in the steady-state current was not accompanied by a change in the deactivation time constant and thus, is more likely to result from a change in desensitization than a slowing of channel closing. The results indicate that GYKI 52466 modulates AMPA receptor-mediated currents in a complex manner, perhaps by acting through more than one binding site.
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Department of Pharmacology, Southern Illinois University School of Medicine, P.O. Box 19629, Springfield, IL 62794-9629, USA. aarai@siumed.edu
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D007700:Kinetics; D008297:Male; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects*
D014151:Anti-Anxiety Agents; D018091:Receptors, AMPA; C061950:GYKI 52466; D001569:Benzodiazepines