title: Effects of GYKI 52466 and some 2,3-benzodiazepine derivatives on hippocampal in vitro basal neuronal excitability and 4-aminopyridine epileptic activity.
abstract: In order to determine whether the anticonvulsant effect of 2, 3-benzodiazepines is also displayed in a model of in vitro epilepsy, such as the "epileptiform" hippocampal slice, we studied the effects of 2,3-benzodiazepine 1-(4-aminophenyl)-4-methyl-7, 8-methylenedioxe-5H 2,3-benzodiazepine hydrochloride (GYKI 52466) and some new 2,3-benzodiazepine derivatives on CA1 basal neuronal excitability and on CA1 epileptiform burst activity produced by 4-aminopyridine in rat hippocampal slices. The results showed that GYKI 52466 affected basal neuronal excitability as evidenced by its influence on the magnitude of the CA1 orthodromic-evoked field potentials. 2,3-Benzodiazepines showed their antiepileptic effect also in an in vitro model of experimental epilepsy. The effects of the new 2,3-benzodiazepine derivatives suggest that the methylenedioxidation in positions 7 and 8 of the 2,3-benzodiazepine ring is the main structural modification for the antiepileptic effect of 2,3-benzodiazepines to take place.
authors.affiliation: Laboratorio di Farmacologia, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Marinelli
authors.forename: F
authors.initials: F
authors.lastname: Gatta
authors.forename: S
authors.initials: S
authors.lastname: Sagratella
mesh_terms: D015761:4-Aminopyridine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology*; D001369:Axons / Q000187:drug effects; D001569:Benzodiazepines / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003292:Convulsants / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004594:Electrophysiology; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017661:Receptors, Presynaptic / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
chemical_list: D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D003292:Convulsants; D017661:Receptors, Presynaptic; C061950:GYKI 52466; D001569:Benzodiazepines; D015761:4-Aminopyridine; D014700:Verapamil