Linked Life Data

11804616

Source:http://linkedlifedata.com/resource/pubmed/id/11804616

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-1-23
pubmed:abstractText
The antiepileptic drug riluzole is a use-dependent blocker of voltage-gated Na(+) channels and selectively depresses action potential-driven glutamate over gamma-aminobutyric acid (GABA) release. Here we report that in addition to its presynaptic effect, riluzole at higher concentrations also strongly potentiates postsynaptic GABA(A) responses both in cultured hippocampal neurons and in Xenopus oocytes expressing recombinant receptors. Although peak inhibitory postsynaptic currents (IPSCs) of autaptic hippocampal neurons were inhibited, 20-100 microM riluzole significantly prolonged the decay of IPSCs, resulting in little change in total charge transfer. The effect was dose-dependent and reversible. Riluzole selectively increased miniature IPSC fast and slow decay time constants, without affecting their relative proportions. Miniature IPSC peak amplitude, rise time and frequency were unaffected, indicating a postsynaptic mechanism. In the Xenopus oocyte expression system, riluzole potentiated GABA responses by lowering the EC(50) for GABA activation. Riluzole directly gated a GABA(A) current that was partially blocked by bicuculline and gabazine. Pharmacological experiments suggest that the action of riluzole did not involve a benzodiazepine, barbiturate, or neurosteroid site. Instead, riluzole-induced potentiation was inhibited by the lactone antagonist alpha-isopropyl-alpha-methyl-gamma-butyrolatone (alpha-IMGBL). While most anticonvulsants either block voltage-gated Na(+) channels or potentiate GABA(A) receptors, our results suggest that riluzole may define an advantageous class of anticonvulsants with both effects.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0028-3908
pubmed:author
pubmed:issnType
Print
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
199-209
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:11804616-Animals, pubmed-meshheading:11804616-Cells, Cultured, pubmed-meshheading:11804616-Dose-Response Relationship, Drug, pubmed-meshheading:11804616-Electrophysiology, pubmed-meshheading:11804616-Excitatory Postsynaptic Potentials, pubmed-meshheading:11804616-GABA Agonists, pubmed-meshheading:11804616-GABA Antagonists, pubmed-meshheading:11804616-GABA Modulators, pubmed-meshheading:11804616-GABA-A Receptor Agonists, pubmed-meshheading:11804616-GABA-A Receptor Antagonists, pubmed-meshheading:11804616-Neuroprotective Agents, pubmed-meshheading:11804616-Patch-Clamp Techniques, pubmed-meshheading:11804616-Rats, pubmed-meshheading:11804616-Rats, Sprague-Dawley, pubmed-meshheading:11804616-Receptors, GABA-A, pubmed-meshheading:11804616-Riluzole, pubmed-meshheading:11804616-Synapses, pubmed-meshheading:11804616-Xenopus, pubmed-meshheading:11804616-gamma-Aminobutyric Acid
pubmed:year
2002
pubmed:articleTitle
Neuroprotective agent riluzole potentiates postsynaptic GABA(A) receptor function.
pubmed:affiliation
Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't