Felbamate selectively blocks in vitro hippocampal kainate-induced irreversible electrical changes.
The influence of the anticonvulsant felbamate has been tested on in vitro excitotoxicity induced by treatment of hippocampal slices with elevated concentrations of NMDA, AMPA and kainic acid. For comparison, the effects of the glutamate antagonist 7-chlorokynurenic acid and of the anticonvulsants pentobarbitone and lamotrigine, were also studied. Slice perfusion with 50 microM NMDA or 25 microM AMPA or 12 microM kainic acid produced within 30 min a disappearance or a pronounced irreversible amplitude reduction of the CA1 electrical synaptic responses. Slice perfusion with 1.2-1.6 mM felbamate or 100 microM lamotrigine significantly decreased the incidence of the irreversible disappearance of the CA1 electrical response induced by kainic acid. On the contrary, slice perfusion with the same concentrations of the drugs did not affect the irreversible disappearance of the CA1 electrical response induced by NMDA or AMPA. By contrast, slice perfusion with 100 microM of 7-chlorokynurenic acid significantly prevented the neurotoxic effects induced by both NMDA and kainic acid, while 100 microM of pentobarbitone failed to affect kainic acid-induced neurotoxicity. The different profile of neuroprotection elicited by felbamate with respect to reference drugs indicates that a different mechanism of action than antagonism of NMDA response or potentiation of GABA response underlies the neuroprotectant effects of felbamate.
Longo
R
R
Laboratorio di Farmacologia, Istituto Superiore di Sanità, Roma, Italy.
Domenici
M R
MR
Scotti de Carolis
A
A
Sagratella
S
S
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D004594:Electrophysiology; D000078328:Felbamate; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007608:Kainic Acid / Q000494:pharmacology*; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000077213:Lamotrigine; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014227:Triazines / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D014227:Triazines; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007736:Kynurenic Acid; D010424:Pentobarbital; C057013:7-chlorokynurenic acid; D007608:Kainic Acid; D000077213:Lamotrigine; D000078328:Felbamate