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.

Zopiclone (brand names Zimovane and Imovane) is a nonbenzodiazepine hypnotic agent used in the treatment of insomnia. The therapeutic pharmacological properties of zopiclone include hypnotic, anxiolytic, anticonvulsant, and myorelaxant properties. Zopiclone and benzodiazepines bind to different sites on GABAA-containing receptors, causing an enhancement of the actions of GABA to produce the therapeutic and adverse effects of zopiclone. The metabolite of zopiclone called desmethylzopiclone is also pharmacologically active, although it has predominately anxiolytic properties. One study found some slight selectivity for zopiclone on α1 and α5 subunits, although it is regarded as being unselective in its binding to α1, α2, α3, and α5 GABAA benzodiazepine receptor complexes. Desmethylzopiclone has been found to have partial agonist properties, unlike the parent drug zopiclone, which is a full agonist. The mechanism of action of zopiclone is similar to benzodiazepines, with similar effects on locomotor activity and on dopamine and serotonin turnover. A meta-analysis of randomised controlled clinical trials that compared benzodiazepines to zopiclone or other Z drugs such as zolpidem and zaleplon has found few clear and consistent differences between zopiclone and the benzodiazepines in sleep onset latency, total sleep duration, number of awakenings, quality of sleep, adverse events, tolerance, rebound insomnia, and daytime alertness. After oral administration, zopiclone is rapidly absorbed, with a bioavailability around 75–80%. Time to peak plasma concentration is 1–2 hours. High-fat meal preceding zopiclone administration does not change absorption (as measured by AUC), but reduces peak plasma levels and delays its occurrence, thus may delay the onset of therapeutic effects. The pharmacokinetics of zopiclone in humans are stereoselective. After oral administration of the racemic mixture, Cmax (time to maximum plasma concentration), area under the plasma time-concentration curve (AUC) and terminal elimination half-life values are higher for the dextrorotatory enantiomers, owing to the slower total clearance and smaller volume of distribution (corrected by the bioavailability), compared with the levorotatory enantiomer. In urine, the concentrations of the dextrorotatory enantiomers of the N-dimethyl and N-oxide metabolites are higher than those of the respective antipodes. Zopiclone is sometimes used as a method of suicide. It has a similar fatality index to that of benzodiazepine drugs, apart from temazepam, which is particularly toxic in overdose.

(R)-Zopiclone is the (R)-enantiomer of benzodiazepine modulator Zopiclone. (S)-Zopiclone binding at benzodiazepine recognition sites is about 50-fold higher than of the (R)-zopiclone, and the pharmacokinetics of the enantiomers varies between individuals differently. In rats, there is no stereo conversion from (S)- to (R)-Zopiclone, whereas (R)-Zopiclone converts to (S)-Zopiclone, which is preferentially distributed into the brain. (R)-Zopiclone is known to have sedative and anxiolytic effects and as well as effects towards locomotor activity reduction.