Effect of flumazenil on GABAA receptors in isolated rat hippocampal neurons.
Using whole cell patch-clamp recordings from pyramidal cells acutely dissociated from rat hippocampal slices, Ro-15 1788 (flumazenil, FLU) was shown to enhance the GABAA-receptor mediated currents evoked by application of gamma-aminobutyric acid (GABA) and to antagonize the enhancing effect of the benzodiazepine agonist flurazepam (FZP) on the GABAA response. Both FLU and FZP increased the peak and the steady-state components of the responses and accelerated the current decay. This suggests that both agents act via a common mechanism on GABA transmission. It is concluded that FLU possesses high affinity for the binding site, but low efficacy on the GABAA-benzodiazepine receptor. This suggests that FLU acts as a partial agonist on GABAA receptors.
Weiss
Michel
M
Laboratoire de physiopathologie et action thérapeutique des gaz sous pression, EA 3280, Université de la Méditerranée et IMNSSA, Faculté de Médecine Nord, IFR Jean Roche, 13916 Marseille, cedex 20, France. drpmweiss@aol.com
Tikhonov
Denis
D
Buldakova
Svetlana
S
D000818:Animals; D005442:Flumazenil / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism
D018757:GABA Modulators; D011963:Receptors, GABA-A; D005442:Flumazenil