Effects of anticonvulsants on spontaneous epileptiform activity which develops in the absence of chemical synaptic transmission in hippocampal slices.
Spontaneous epileptiform activity (SEA) develops in area CA1 of hippocampal slices, when the Ca2+ concentration in the perfusate is lowered to 0.2 mM, at which level evoked chemical synaptic transmission is blocked. We investigated the effects of different anticonvulsants on this autonomous activity, in order to determine whether the antiepileptic effect can be ascribed to an influence on neuronal excitability. Carbamazepine was the most effective to block SEA at concentrations of 1-15 microM. Phenobarbital and phenytoin depressed SEA at concentrations of 25 microM. Valproate was effective at concentrations of 2-5 mM. Midazolam, a water-soluble benzo-diazepine agonist and the N-methyl-D-aspartate antagonists, DL-alpha-aminoadipic acid and 2-amino-7-phosphonoheptanoic acid were ineffective in blocking SEA suggesting that they exert their antiepileptic action by interference with synaptic mechanisms.
Heinemann
U
U
Franceschetti
S
S
Hamon
B
B
Konnerth
A
A
Yaari
Y
Y
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology; D002220:Carbamazepine / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D004827:Epilepsy / Q000188:drug therapy*; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008874:Midazolam; D010634:Phenobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D051381:Rats; D014635:Valproic Acid / Q000494:pharmacology
D000927:Anticonvulsants; D007473:Ion Channels; D001569:Benzodiazepines; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin; D008874:Midazolam; D010634:Phenobarbital