Eszopiclone is a nonbenzodiazepine hypnotic, pyrrolopyrazine derivative of the cyclopyrrolone class and is indicated for the short-term treatment of insomnia. While Eszopiclone is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with the gamma-aminobutyric acid-benzodiazepine (GABABZ) receptor complex. Subunit modulation of the GABABZ receptor chloride channel macromolecular complex is hypothesized to be responsible for some of the pharmacological properties of benzodiazepines, which include sedative, anxiolytic, muscle relaxant, and anticonvulsive effects in animal models. Eszopiclone binds selectively to the brain alpha subunit of the GABA A omega-1 receptor. The mechanism of action of Eszopiclone is not completely understood. It is thought that Eszopiclone acts on the benzodiazepine receptors as an agonist and interacts with GABA-receptor complexes. Used for the treatment of insomnia.

Fumazenil is an imidazobenzodiazepine derivative and a potent benzodiazepine receptor antagonist that competitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex, thereby reversing the effects of benzodiazepine on the central nervous system. Fumazenil is used for the complete or partial reversal of the sedative effects of benzodiazepines in cases where general anesthesia has been induced and/or maintained with benzodiazepines, and where sedation has been produced with benzodiazepines for diagnostic and therapeutic procedures. Also for the management of benzodiazepine overdose as an adjunct for appropriate supportive and symptomatic measures. Flumazenil went off patent in 2008 so at present generic formulations of this drug are available.

MRK-409 (MK-0343) is a subtype-selective GABA(A) partial agonist that occupies the benzodiazepine site of GABA(A) receptors. MK-0343 was designed to be a less sedating anxiolytic, based on reduced efficacy at the alpha-1 subtype and significant efficacy at alpha -2 and alpha-3 subtypes of the GABA(A) receptor. MRK-409 binds to alpha-1, 2, 3 and 5-containing human recombinant GABA(A) receptors with comparable high affinity (0.21-0.40 nM). However, MRK-409 has greater agonist efficacy at the alpha-3 compared with alpha-1 subtypes. MRK-409 exhibited anxiolytic and non-sedating properties in different rodent and primate models of unconditioned and conditioned models of anxiety but produced sedation in man at relatively low levels of GABA(A) receptor occupancy (∼10%). It was suggested that the sedation with MRK-409 was due to the partial agonist efficacy of that compound at the alpha-1 subtype. Although MRK-409 (MK-0343) reached clinical studies its development had to be stopped due to sedative effects in humans demonstrated that more preclinical efforts are needed to identify compounds with improved selectivity.

L-822179 is a triazolophthalazine that selectively attenuates the effects of GABA at GABA(A) receptors containing an alpha5 subunit. It is an orally active, functionally selective compound, which enhances cognition in animals without anxiogenic or convulsant effects. The dose-limiting adverse event of L-822179 is dizziness and/or light-headedness. L-822179 does not improve cognitive performance in the elderly; indeed the dose of 4 mg actually significantly impairs performance. In this regard, it could therefore be considered that this study is a failed trial in so far as the positive control, lorazepam, does not show the anticipated effect.

L-822179 is a triazolophthalazine that selectively attenuates the effects of GABA at GABA(A) receptors containing an alpha5 subunit. It is an orally active, functionally selective compound, which enhances cognition in animals without anxiogenic or convulsant effects. The dose-limiting adverse event of L-822179 is dizziness and/or light-headedness. L-822179 does not improve cognitive performance in the elderly; indeed the dose of 4 mg actually significantly impairs performance. In this regard, it could therefore be considered that this study is a failed trial in so far as the positive control, lorazepam, does not show the anticipated effect.