|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||399.397 g/mol g·mol−1|
|3D model (JSmol)|
|(what is this?)|
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.
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- Mirza NR, Rodgers RJ, Mathiasen LS (2006). "Comparative cue generalization profiles of L-838, 417, SL651498, zolpidem, CL218,872, ocinaplon, bretazenil, zopiclone, and various benzodiazepines in chlordiazepoxide and zolpidem drug discrimination". J. Pharmacol. Exp. Ther. 316 (3): 1291–9. doi:10.1124/jpet.105.094003. PMID 16339395.
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