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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. 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. It substitutes fully for the anxiolytic benzodiazepine chlordiazepoxide, but only partially substituted for the imidazopyridine hypnotic drug zolpidem and the benzodiazepine hypnotic triazolam. When given repeatedly it failed to produce tolerance or dependence, probably due to its low affinity and efficacy at the α5 subtype.
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. 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.
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