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Epilepsy Res. 1992 Apr;11(2):75-88.

In vitro studies on the broad spectrum anticonvulsant loreclezole in the hippocampus.

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  • 1Department of Neuropsychopharmacology, Janssen Research Foundation, Beerse, Belgium.

Abstract

In hippocampal slices from guinea-pig a paired-pulse stimulation protocol was used to examine the effects of loreclezole, R-(+)-etomidate, phenobarbital and pentobarbital on orthodromic and antidromic GABAergic neuronal inhibition in the CA1 region. All four compounds increased orthodromic GABAergic inhibition, with R-(+)-etomidate and pentobarbital inducing a quantitatively larger effect than loreclezole and phenobarbital. Only R-(+)-etomidate and pentobarbital increased antidromic GABAergic inhibition. We propose that all four compounds are anticonvulsant by increasing feed-forward dendritic GABAergic inhibition, whilst only the sedative/hypnotic compounds (R-(+)-etomidate, pentobarbital) increase feedback recurrent GABAergic inhibition. Loreclezole was also shown to inhibit 'low Ca2+' and 'low Mg2+' epileptogenesis at similar concentrations to those active on inhibition. Thus loreclezole may possess other pharmacodynamic properties, beyond its ability to increase feed-forward GABAergic neuronal inhibition, which contribute to its antiepileptic action.

PMID:
1618181
[PubMed - indexed for MEDLINE]
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