L-838,417 is a subtype-selective GABAApositive 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.
^McKernan RM, Rosahl TW, Reynolds DS, et al. (2000). "Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA(A) receptor alpha1 subtype". Nat. Neurosci. 3 (6): 587–92. doi:10.1038/75761. PMID10816315.
^Atack JR (2005). "The benzodiazepine binding site of GABA(A) receptors as a target for the development of novel anxiolytics". Expert Opin Investig Drugs. 14 (5): 601–18. doi:10.1517/135437184.108.40.2061. PMID15926867.
^Ujfalussy B, Kiss T, Orbán G, Hoffmann WE, Erdi P, Hajós M (2007). "Pharmacological and computational analysis of alpha-subunit preferential GABA(A) positive allosteric modulators on the rat septo-hippocampal activity". Neuropharmacology. 52 (3): 733–43. doi:10.1016/j.neuropharm.2006.09.022. PMID17113111.
^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. PMID16339395.
^Mathiasen L, Mirza NR (2005). "A comparison of chlordiazepoxide, bretazenil, L838,417 and zolpidem in a validated mouse Vogel conflict test". Psychopharmacology. 182 (4): 475–84. doi:10.1007/s00213-005-0119-z. PMID16133136.
^Carling RW, Madin A, Guiblin A, et al. (2005). "7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine: a functionally selective gamma-aminobutyric acid(A) (GABA(A)) alpha2/alpha3-subtype selective agonist that exhibits potent anxiolytic activity but is not sedating in animal models". J. Med. Chem. 48 (23): 7089–92. doi:10.1021/jm058034a. PMID16279764.