Systematic (IUPAC) name
Clinical data
Legal status
CAS number  N
ATC code ?
ChemSpider  YesY
Chemical data
Formula C23H20FN3O2 
Mol. mass 389.421 g/mol

SL-651,498 is an anxiolytic and anticonvulsant drug used in scientific research, with a chemical structure most closely related to β-carboline derivatives such as abecarnil and gedocarnil.[1] It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic.

SL-651,498 is a subtype-selective GABAA agonist, which acts as a full agonist at α2 and α3 subtypes, and as a partial agonist at α1 and α5 (although its action at α5 subtypes is much weaker than at the others). In animal studies, it has primarily anxiolytic effects, although some sedation, ataxia and muscle relaxant effects are observed at higher doses.[2] It substitutes fully for the anxiolytic benzodiazepine chlordiazepoxide, but only partially substituted for the imidazopyridine hypnotic drug zolpidem and the benzodiazepine hypnotic triazolam.[3][4] When given repeatedly it failed to produce tolerance or dependence, probably due to its low affinity and efficacy at the α5 subtype.[5]

SL-651,498 has been suggested for development as a novel non-sedating anxiolytic drug for humans, although it is still only at an early stage of research.[6] Preliminary human trials suggest similar efficacy to lorazepam as an anxiolytic, but with little or no sedation or impairment of memory, motor skills or cognitive function.[7]

There are other possibly anxioselective compounds in development, such as L-838,417, NGD 91-3.[8]


  1. ^ Sevrin M, Maloizel C, Evanno Y, Legalloudec O, George P. (Sanofi-Synthelabo). 1H-Pyrido[3,4-b]indole-4-carboxamide derivatives, preparation and application thereof in therapeutics. US Patent 6075021
  2. ^ Griebel G, Perrault G, Simiand J, Cohen C, Granger P, Depoortere H, Françon D, Avenet P, Schoemaker H, Evanno Y, Sevrin M, George P, Scatton B. SL651498, a GABAA receptor agonist with subtype-selective efficacy, as a potential treatment for generalized anxiety disorder and muscle spasms. CNS Drug Reviews. 2003 Spring;9(1):3-20.
  3. ^ Griebel G, Perrault G, Simiand J, Cohen C, Granger P, Decobert M, Françon D, Avenet P, Depoortere H, Tan S, Oblin A, Schoemaker H, Evanno Y, Sevrin M, George P, Scatton B. SL651498: an anxioselective compound with functional selectivity for alpha2- and alpha3-containing gamma-aminobutyric acid(A) (GABA(A)) receptors. Journal of Pharmacology and Experimental Therapeutics. 2001 Aug;298(2):753-68.
  4. ^ Licata SC, Platt DM, Cook JM, Sarma PV, Griebel G, Rowlett JK. Contribution of GABAA receptor subtypes to the anxiolytic-like, motor, and discriminative stimulus effects of benzodiazepines: studies with the functionally selective ligand SL651498 [6-fluoro-9-methyl-2-phenyl-4-(pyrrolidin-1-yl-carbonyl)-2,9-dihydro-1H-pyridol[3,4-b]indol-1-one]. Journal of Pharmacology and Experimental Therapeutics. 2005 Jun;313(3):1118-25.
  5. ^ Mirza NR, Nielsen EØ. Do subtype-selective gamma-aminobutyric acid A receptor modulators have a reduced propensity to induce physical dependence in mice? Journal of Pharmacology and Experimental Therapeutics. 2006 Mar;316(3):1378-85.
  6. ^ Whiting PJ. GABA-A receptors: a viable target for novel anxiolytics? Current Opinion in Pharmacology. 2006 Feb;6(1):24-9.
  7. ^ S L de Haas, K L Franson, J A J Schmitt, A F Cohen, J B Fau, C Dubruc, and J M A van Gerven. The pharmacokinetic and pharmacodynamic effects of SL65.1498, a GABA-A 2,3 selective agonist, in comparison with lorazepam in healthy volunteers. Journal of Psychopharmacology published online July 17, 2008.
  8. ^ Atack JR (August 2003). "Anxioselective compounds acting at the GABA(A) receptor benzodiazepine binding site". Curr Drug Targets CNS Neurol Disord. 2 (4): 213–12.