L 838,417

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 GABA_A 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.