Document Detail


Felbamate selectively blocks in vitro hippocampal kainate-induced irreversible electrical changes.
MedLine Citation:
PMID:  7537844     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
R Longo; M R Domenici; A Scotti de Carolis; S Sagratella
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Life sciences     Volume:  56     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  1995  
Date Detail:
Created Date:  1995-06-05     Completed Date:  1995-06-05     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  PL409-14     Citation Subset:  IM    
Affiliation:
Laboratorio di Farmacologia, Istituto Superiore di Sanità, Roma, Italy.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anticonvulsants / pharmacology
Electrophysiology
Hippocampus / drug effects*,  physiology
Kainic Acid / pharmacology*
Kynurenic Acid / analogs & derivatives,  pharmacology
Male
N-Methylaspartate / pharmacology
Pentobarbital / pharmacology
Phenylcarbamates
Propylene Glycols / pharmacology*
Rats
Rats, Wistar
Triazines / pharmacology
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology
Chemical
Reg. No./Substance:
0/Anticonvulsants; 0/Phenylcarbamates; 0/Propylene Glycols; 0/Triazines; 18000-24-3/7-chlorokynurenic acid; 25451-15-4/felbamate; 487-79-6/Kainic Acid; 492-27-3/Kynurenic Acid; 6384-92-5/N-Methylaspartate; 76-74-4/Pentobarbital; 77521-29-0/alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; 84057-84-1/lamotrigine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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