title: Inhibitory effects of N-valproyl-L-tryptophan on high potassium, low calcium and low magnesium-induced CA1 hippocampal epileptiform bursting activity in rat brain slices.
abstract: N-valproyl-L-tryptophan (VPA-Tryp), new antiepileptic drug, was tested on CA1 hippocampal epileptiform bursting activity obtained by increasing potassium and lowering calcium and magnesium concentrations in the fluid perfusing rat brain slices. Each slice was treated with a single concentration (0.2, 0.5, 1 or 2 mM) of Valproate (VPA) or VPA-Tryp. Both burst duration and interburst frequency during and after treatment were off-line compared with baseline values. For both parameters, the latency and the length of statistically significant response periods as well as the magnitude of drug-induced responses were calculated. VPA-Tryp evoked fewer and weaker early excitatory effects than VPA on bursting activity. On the contrary, VPA-Tryp induced powerful and long-lasting inhibitory effects on epileptiform discharge in a significantly higher number of slices than VPA. In fact, greater length and magnitude of VPA-Tryp-induced inhibition on both interburst frequency and burst duration were observed. Furthermore, VPA-Tryp showed antiepileptic activity at lower concentration than VPA and, when testing both drugs at analogue concentrations, VPA-Tryp evoked responses with either shorter latency or greater effect length and magnitude than VPA.
authors.affiliation: Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Sezione di Fisiologia umana "G. Pagano", Università degli Studi di Palermo, Corso Tukory 129, 90134 Palermo, Italy. pierangelo.sardo@unipa.it
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Sardo
authors.forename: Valerio
authors.initials: V
authors.lastname: Rizzo
authors.forename: Simonetta
authors.initials: S
authors.lastname: Friscia
authors.forename: Fabio
authors.initials: F
authors.lastname: Carletti
authors.forename: Viviana
authors.initials: V
authors.lastname: De Caro
authors.forename: Anna Lisa
authors.initials: AL
authors.lastname: Scaturro
authors.forename: Giulia
authors.initials: G
authors.lastname: Giandalia
authors.forename: Libero Italo
authors.initials: LI
authors.lastname: Giannola
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ferraro
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D056547:CA1 Region, Hippocampal / Q000187:drug effects*; D004151:Dipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects
chemical_list: D000927:Anticonvulsants; D004151:Dipeptides; C558142:N-valproyl-L-tryptophan; D008274:Magnesium; D011188:Potassium