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Antagonists of GLU(K5)-containing kainate receptors prevent pilocarpine-induced limbic seizures.

Authors: Smolders, I  Bortolotto, ZA  Clarke, VR  Warre, R  Khan, GM  O'Neill, MJ  Ornstein, PL  Bleakman, D  Ogden, A  Weiss, B  Stables, JP  Ho, KH  Ebinger, G  Collingridge, GL  Lodge, D  Michotte, Y 
Citation: Smolders I, etal., Nat Neurosci 2002 Aug;5(8):796-804.
Pubmed: (View Article at PubMed) PMID:12080343
DOI: Full-text: DOI:10.1038/nn880

Developments in the molecular biology and pharmacology of GLU(K5), a subtype of the kainate class of ionotropic glutamate receptors, have enabled insights into the roles of this subunit in synaptic transmission and plasticity. However, little is known about the possible functions of GLU(K5)-containing kainate receptors in pathological conditions. We report here that, in hippocampal slices, selective antagonists of GLU(K5)-containing kainate receptors prevented development of epileptiform activity--evoked by the muscarinic agonist, pilocarpine--and inhibited the activity when it was pre-established. In conscious rats, these GLU(K5) antagonists prevented and interrupted limbic seizures induced by intra-hippocampal pilocarpine perfusion, and attenuated accompanying rises in extracellular L-glutamate and GABA. This anticonvulsant activity occurred without overt side effects. GLU(K5) antagonism also prevented epileptiform activity induced by electrical stimulation, both in vitro and in vivo. Therefore, we propose that subtype-selective GLU(K5) kainate receptor antagonists offer a potential new therapy for epilepsy.


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RGD Object Information
RGD ID: 625595
Created: 2002-10-11
Species: All species
Last Modified: 2002-10-11
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.