The effects of flumazenil on focal, electroinduced after-discharge in rabbits.
1. The anticonvulsive efficacy of flumazenil 10 mg/kg i.v., a BDZ antagonist, was studied in two models of experimental epilepsy electrically induced. 2. The EEG after-discharge, which was induced by the electrical stimulation of selected brain regions [(notably the dorsal hippocampus (Hip) and the amygdala (CAm)] was evaluated in rabbits pre- and post-drug administration. 3. In the animals submitted to electrical stimulation of the amygdala, flumazenil exerted a protective action, thereby inducing an increase in the after-discharge threshold and/or a decrease in after-discharge duration. 4. In the animals submitted to electrical stimulation of the hippocampus, flumazenil did not induced changes statistically significant. 5. Finally, the paper discusses the two possible mechanisms of action of flumazenil (a "per se" partial BDZ activity and/or a BDZ agonistic activity, which displaces the inverse agonist-like ligand) and the differencies in GABA distribution in the hippocampus and the amygdala.
Bo
P
P
Neurological Institute C. Mondino, Pavia, Italy.
Soragna
D
D
Marchioni
E
E
Albergati
A
A
Candeloro
E
E
Savoldi
F
F
D000679:Amygdala / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000037:antagonists & inhibitors; D001921:Brain / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D004558:Electric Stimulation; D004569:Electroencephalography / Q000187:drug effects; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D005442:Flumazenil / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D008297:Male; D011817:Rabbits
D000927:Anticonvulsants; D001569:Benzodiazepines; D005442:Flumazenil