Electrophysiological actions of felbamate on rat striatal neurones.
1. We have investigated the effects of the anticonvulsant drug, felbamate (FBM), on striatal neurones, recorded in vitro by using both intracellular and extracellular conventional recordings in slices and whole-cell recordings in acutely isolated neurones. 2. FBM, at therapeutically relevant concentrations (30-300 microM) showed multiple mechanisms of action. Like other antiepileptic drugs, FBM (30-300 microM) showed a direct inhibitory action on current-evoked firing discharge of striatal neurones. A patch-clamp analysis of this effect revealed a dose-related reduction of voltage-dependent sodium (Na+) currents (10-100 microM), with a half inhibiton dose (IC50) value of 28 microM. 3. We also tested whether FBM affected corticostriatal glutamate transmission. In control medium (1.2 mM external magnesium), both extracellularly recorded field potentials and intracellularly recorded excitatory postsynaptic potentials (e.p.s.ps) evoked by cortical stimulation were no affected by bath application of 30-300 microM FBM. 4. When magnesium was removed from the perfusing solution, a procedure which reveals a N-methyl-D-aspartate (NMDA)-mediated component in the corticostriatal synaptic potential, FBM (30-300 microM) produced a dose-dependent reduction of the amplitude of both the field potential and the e.p.s.p. 5. FBM reduced the inward currents produced either by bath or by focal applications of 30 microM NMDA, finding consistent with the hypothesis that the observed reduction of the NMDA-mediated component of the synaptic potentials may be caused at postsynaptic level. 6. The reduction of the NMDA-mediated component of the synaptic transmission by FBM and its depressant effect on the voltage-dependent Na+ channels, may account for the antiepileptic action of this drug. Moreover, the pharmacological properties of FBM might render this drug interesting as a neuroprotectant agent.
Pisani
A
A
Dip. Sanità e Biologia Cellulare, Università di Roma Tor Vergata, Roma, Italy.
Stefani
A
A
Siniscalchi
A
A
Mercuri
N B
NB
Bernardi
G
G
Calabresi
P
P
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018846:Excitatory Amino Acids / Q000378:metabolism; D000078328:Felbamate; D008297:Male; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D000927:Anticonvulsants; D018846:Excitatory Amino Acids; D048448:Phenylcarbamates; D011409:Propylene Glycols; D016194:Receptors, N-Methyl-D-Aspartate; D000078328:Felbamate