L-655,708

L-655,708 (also known as FG-8094) is a potent, selective negative allosteric modulator (inverse agonist) of GABAA receptors containing the α5 subunit (Ki = 0.45 nM). It was originally developed by Merck Sharp & Dohme (now Merck & Co.) as a cognitive enhancer (nootropic). It exhibits 50- to 100-fold binding selectivity for α5-containing GABAA receptors over those containing α1, α2, or α3 subunits. Although it demonstrated cognitive-enhancing properties in animal models, its development was discontinued due to anxiogenic side effects at active doses. It remains widely used as a pharmacological research tool to study GABAA receptor function, synaptic plasticity, learning, memory, and rapid-acting antidepressant mechanisms.

Other names

11,12,13,13a-tetrahydro-7-methoxy-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylic acid, ethyl esterethyl (13aS)-7-methoxy-9-oxo-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylateethyl (S)-11,12,13,13a-tetrahydro-7-methoxy-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate