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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2004-10-15
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pubmed:abstractText |
Clinically used benzodiazepine and nonbenzodiazepine sedative-hypnotic agents for the treatment of insomnia produce their therapeutic effects through allosteric enhancement of the effects of the inhibitory neurotransmitter GABA at the GABA(A) receptor. Indiplon is a novel pyrazolopyrimidine sedative-hypnotic agent, currently in development for insomnia. Using radioligand binding studies, indiplon inhibited the binding of [(3)H]Ro 15-1788 (flumazenil) to rat cerebellar and cerebral cortex membranes with high affinity (K(i) values of 0.55 and 0.45 nM, respectively). [(3)H]Indiplon binding to rat cerebellar and cerebral cortex membranes was reversible and of high affinity, with K(D) values of 1.01 and 0.45 nM, respectively, with a pharmacological specificity consistent with preferential labeling of GABA(A) receptors containing alpha1 subunits. In "GABA shift" experiments and in measurements of GABA-induced chloride conductance in rat cortical neurons in culture, indiplon behaved as an efficacious potentiator of GABA(A) receptor function. In both the radioligand binding and electrophysiological experiments, indiplon had a higher affinity than zolpidem or zaleplon. These in vitro properties are consistent with the in vivo properties of indiplon as an effective sedative-hypnotic acting through allosteric potentiation of the GABA(A) receptor.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acetamides,
http://linkedlifedata.com/resource/pubmed/chemical/Azides,
http://linkedlifedata.com/resource/pubmed/chemical/Benzodiazepines,
http://linkedlifedata.com/resource/pubmed/chemical/Chloride Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Flumazenil,
http://linkedlifedata.com/resource/pubmed/chemical/GABA Modulators,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, GABA-A,
http://linkedlifedata.com/resource/pubmed/chemical/Ro 15-4513,
http://linkedlifedata.com/resource/pubmed/chemical/Thiophenes,
http://linkedlifedata.com/resource/pubmed/chemical/Triazolam,
http://linkedlifedata.com/resource/pubmed/chemical/Tritium,
http://linkedlifedata.com/resource/pubmed/chemical/gamma-Aminobutyric Acid,
http://linkedlifedata.com/resource/pubmed/chemical/indiplon,
http://linkedlifedata.com/resource/pubmed/chemical/zaleplon,
http://linkedlifedata.com/resource/pubmed/chemical/zolpidem
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0022-3565
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
311
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
537-46
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15256540-Acetamides,
pubmed-meshheading:15256540-Animals,
pubmed-meshheading:15256540-Azides,
pubmed-meshheading:15256540-Benzodiazepines,
pubmed-meshheading:15256540-Binding Sites,
pubmed-meshheading:15256540-Brain,
pubmed-meshheading:15256540-Cell Membrane,
pubmed-meshheading:15256540-Cerebellum,
pubmed-meshheading:15256540-Cerebral Cortex,
pubmed-meshheading:15256540-Chloride Channels,
pubmed-meshheading:15256540-Flumazenil,
pubmed-meshheading:15256540-GABA Modulators,
pubmed-meshheading:15256540-Kinetics,
pubmed-meshheading:15256540-Male,
pubmed-meshheading:15256540-Pyridines,
pubmed-meshheading:15256540-Pyrimidines,
pubmed-meshheading:15256540-Rats,
pubmed-meshheading:15256540-Rats, Sprague-Dawley,
pubmed-meshheading:15256540-Receptors, GABA-A,
pubmed-meshheading:15256540-Thiophenes,
pubmed-meshheading:15256540-Triazolam,
pubmed-meshheading:15256540-Tritium,
pubmed-meshheading:15256540-gamma-Aminobutyric Acid
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pubmed:year |
2004
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pubmed:articleTitle |
Characterization of the interaction of indiplon, a novel pyrazolopyrimidine sedative-hypnotic, with the GABAA receptor.
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pubmed:affiliation |
Department of Pharmacology, Neurocrine Biosciences Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
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pubmed:publicationType |
Journal Article
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