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 r e-examined the effects of GYKI 52466 on AMPA receptor-mediated currents in patches excised from pyramidal neurons in the hippocampal CA1 field and fou nd that this drug has positive modulatory effects in addition to ifs recept or blocking action. A low concentration of GYKI 52466 (10 muM) reliably inc reased the steady-state current by about three-fold. while the peak current was reduced by 30% only. Higher drug concentrations produced parallel redu ctions in both the steady-state and peak currents. The increase in the stea dy-state current was not accompanied by a change in the deactivation time c onstant and thus, is more likely to result from a change in desensitization than a slowing of channel closing. The results indicate that GYKI 52466 mo dulates AMPA receptor-mediated currents in a complex manner, perhaps by act ing through more than one binding site. (C) 2001 Elsevier Science B.V. All rights reserved.