L-838,417 (original) (raw)
L-838,417 is an anxiolytic drug used in scientific research. It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic. The compound was developed by Merck, Sharp and Dohme. As might be predicted from its binding profile, L-838,417 substitutes for the anxiolytic benzodiazepine chlordiazepoxide in animals, but not for the hypnotic imidazopyridine drug zolpidem. The synthesis of L-838,417 and similar compounds was described in 2005 in the Journal of Medicinal Chemistry.
| Property | Value |
|---|---|
| dbo:abstract | L-838,417 is an anxiolytic drug used in scientific research. It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic. The compound was developed by Merck, Sharp and Dohme. L-838,417 is a subtype-selective GABAA positive allosteric modulator, acting as a partial agonist at α2, α3 and α5 subtypes. However, it acts as a negative allosteric modulator at the α1 subtype, and has little affinity for the α4 or α6 subtypes. This gives it selective anxiolytic effects, which are mediated mainly by α2 and α3 subtypes, but with little sedative or amnestic effects as these effects are mediated by α1. Some sedation might still be expected due to its activity at the α5 subtype, which can also cause sedation, however no sedative effects were seen in animal studies even at high doses, suggesting that L-838,417 is primarily acting at α2 and α3 subtypes with the α5 subtype of lesser importance. As might be predicted from its binding profile, L-838,417 substitutes for the anxiolytic benzodiazepine chlordiazepoxide in animals, but not for the hypnotic imidazopyridine drug zolpidem. The synthesis of L-838,417 and similar compounds was described in 2005 in the Journal of Medicinal Chemistry. In neuropathic pain animal models, it has been shown that stabilizing the Potassium Chloride Cotranspoter 2 (KCC2) at neuronal membranes could not only potentiate the L-838,417-induced analgesia in rats, but also rescue its analgesic potential at high doses, revealing a novel strategy for analgesia in pathological pain, by combined targeting of the appropriate GABAA receptor subtypes (i.e. α2, α3) and restoring Cl− homeostasis. (en) |
| dbo:casNumber | 286456-42-6 |
| dbo:chEMBL | 373250 |
| dbo:fdaUniiCode | 8CZO0970G3 |
| dbo:pubchem | 9908880 |
| dbo:thumbnail | wiki-commons:Special:FilePath/L-838,417.svg?width=300 |
| dbo:wikiPageID | 14568730 (xsd:integer) |
| dbo:wikiPageLength | 8883 (xsd:nonNegativeInteger) |
| dbo:wikiPageRevisionID | 1082816714 (xsd:integer) |
| dbo:wikiPageWikiLink | dbr:Partial_agonist dbr:Benzodiazepine dbr:Α5IA dbr:KCC2 dbc:Ethers dbc:Fluoroarenes dbc:GABAA_receptor_positive_allosteric_modulators dbc:Triazoles dbr:GABRA3 dbr:Anxiolytic dbr:Zolpidem dbr:Positive_allosteric_modulator dbr:GABAA_receptor dbr:GABRA2 dbr:GABRA4 dbr:GABRA5 dbr:GABRA6 dbc:Anxiolytics dbr:Nonbenzodiazepine dbr:Journal_of_Medicinal_Chemistry dbc:Tert-butyl_compounds dbr:Hypnotic dbr:Chlordiazepoxide dbc:Triazolopyridazines dbr:Merck_Sharp_and_Dohme dbr:Sedative dbr:Imidazopyridine dbr:SL-651,498 dbr:Amnestic dbr:GABA_A_receptor dbr:GABRA1 dbr:Negative_allosteric_modulator |
| dbp:alt | Ball-and-stick model of the L-838,417 molecule (en) |
| dbp:c | 19 (xsd:integer) |
| dbp:casNumber | 286456 (xsd:integer) |
| dbp:chembl | 373250 (xsd:integer) |
| dbp:chemspiderid | 8084532 (xsd:integer) |
| dbp:f | 2 (xsd:integer) |
| dbp:h | 19 (xsd:integer) |
| dbp:image | L-838,417 3D ball.png (en) |
| dbp:iupacName | 3 (xsd:integer) |
| dbp:iupharLigand | 4241 (xsd:integer) |
| dbp:n | 7 (xsd:integer) |
| dbp:o | 1 (xsd:integer) |
| dbp:pubchem | 9908880 (xsd:integer) |
| dbp:smiles | CN1N=CN=C1COC4=NN2C=NN=C2C3=CC=CC=C3F (en) |
| dbp:stdinchi | 1 (xsd:integer) |
| dbp:stdinchikey | BQDUNOMMYOKHEP-UHFFFAOYSA-N (en) |
| dbp:unii | 8 (xsd:integer) |
| dbp:verifiedfields | changed (en) |
| dbp:verifiedrevid | 461942177 (xsd:integer) |
| dbp:width | 250 (xsd:integer) |
| dbp:wikiPageUsesTemplate | dbt:Drugbox dbt:GABAAR_PAMs dbt:Short_description dbt:Cascite dbt:Chemspidercite dbt:Drugbankcite dbt:Ebicite dbt:Fdacite dbt:Stdinchicite dbt:Anxiolytics |
| dcterms:subject | dbc:Ethers dbc:Fluoroarenes dbc:GABAA_receptor_positive_allosteric_modulators dbc:Triazoles dbc:Anxiolytics dbc:Tert-butyl_compounds dbc:Triazolopyridazines |
| gold:hypernym | dbr:Drug |
| rdf:type | owl:Thing dul:ChemicalObject dbo:ChemicalSubstance wikidata:Q8386 yago:Abstraction100002137 yago:Element114840755 yago:Matter100020827 yago:Part113809207 yago:PhysicalEntity100001930 yago:Quintessence114847103 yago:Relation100031921 dbo:Drug yago:Substance100019613 yago:WikicatEthers umbel-rc:DrugProduct |
| rdfs:comment | L-838,417 is an anxiolytic drug used in scientific research. It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic. The compound was developed by Merck, Sharp and Dohme. As might be predicted from its binding profile, L-838,417 substitutes for the anxiolytic benzodiazepine chlordiazepoxide in animals, but not for the hypnotic imidazopyridine drug zolpidem. The synthesis of L-838,417 and similar compounds was described in 2005 in the Journal of Medicinal Chemistry. (en) |
| rdfs:label | L-838,417 (en) |
| owl:sameAs | freebase:L-838,417 yago-res:L-838,417 wikidata:L-838,417 dbpedia-sh:L-838,417 dbpedia-sr:L-838,417 dbpedia-vi:L-838,417 https://global.dbpedia.org/id/4q8N4 |
| prov:wasDerivedFrom | wikipedia-en:L-838,417?oldid=1082816714&ns=0 |
| foaf:depiction | wiki-commons:Special:FilePath/L-838,417.svg wiki-commons:Special:FilePath/L-838,417_3D_ball.png |
| foaf:isPrimaryTopicOf | wikipedia-en:L-838,417 |
| is dbo:wikiPageWikiLink of | dbr:SL651498 dbr:GABAA_receptor dbr:GABAA_receptor_positive_allosteric_modulator dbr:Nonbenzodiazepine dbr:TP-003 dbr:TP-13 |
| is foaf:primaryTopic of | wikipedia-en:L-838,417 |
