Barbital, the one of the series of barbiturates, has hypnotic, sedative, and anticonvulsant properties and used under the trade name Veronal. It calmed manic patients and helped melancholic patients to sleep and was an effective inducer of sleep in insomniacs, but at the same time compound could induced dependence. It was substituted by the butyl analog, butobarbital, which was three times stronger and its period of action was much shorter due to its lipophilicity. Barbital is a ligand of GABA-receptor complex and in addition, it could have another target, a creatine kinase.

Flunitrazepam is an intermediate-acting benzodiazepine with general properties similar to those of diazepam. It is generally intended to be for short-term treatment for chronic or severe insomniacs who are unresponsive to other hypnotics. The main pharmacological effects of Flunitrazepam are the enhancement of GABA at the GABAA receptor. The physical effects of Flunitrazepam include sedation, muscle relaxation, decreased anxiety, and prevention of convulsions. It causes partial amnesia; individuals are unable to remember certain events that they experience while under the influence of the drug. Chronic use of Flunitrazepam can result in physical dependence and the appearance of a withdrawal syndrome when the drug is discontinued. Flunitrazepam impairs cognitive and psychomotor functions affecting reaction time and driving skill. The use of this drug in combination with alcohol is a particular concern as both central nervous system depressants potentiate each other's toxicity.

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.

Fabomotizole (also known as Afobazole) is a selective non-benzodiazepine anxiolytic which was developed in Russia and launched in 2006. The drug is used for the treatment of wide range of diseases: generalized anxious disorders, neurasthenia, adaptation disorders, sleep disorders, for alleviation of withdrawal syndrome. According to the drug label (in Russian), its action is related to the interaction with sigma-1 receptors.

Chlormethiazole has sedative, hypnotic, anticonvulsant and neuroprotective properties. This drug is approved in different counties under the different brand name (e.g., Heminevrin) and is used for the management of restlessness and agitation in the elderly, short-term treatment of severe insomnia in the elderly and treatment of alcohol withdrawal symptoms. Clomethiazole interacts with the picrotoxin/barbiturate site of the GABAA-receptor-chloride channel complex. Clomethiazole is pharmacologically distinct from both the benzodiazepines and the barbiturates. Given alone its effects on respiration are slight and the therapeutic index high.

Butoctamide (Butoctamide hydrogen succinate, BAHS), which is related to an organic compound naturally occurring in CSF, has been demonstrated to increase REM sleep in cats and young adults. BAHS was confirmed also to increase REM sleep in healthy aged subjects. The drug is marketed under the brand named Listomin S in Japan. It is effective against insomnia and other sleep disorders.

Fabomotizole (also known as Afobazole) is a selective non-benzodiazepine anxiolytic which was developed in Russia and launched in 2006. The drug is used for the treatment of wide range of diseases: generalized anxious disorders, neurasthenia, adaptation disorders, sleep disorders, for alleviation of withdrawal syndrome. According to the drug label (in Russian), its action is related to the interaction with sigma-1 receptors.

Chlormethiazole has sedative, hypnotic, anticonvulsant and neuroprotective properties. This drug is approved in different counties under the different brand name (e.g., Heminevrin) and is used for the management of restlessness and agitation in the elderly, short-term treatment of severe insomnia in the elderly and treatment of alcohol withdrawal symptoms. Clomethiazole interacts with the picrotoxin/barbiturate site of the GABAA-receptor-chloride channel complex. Clomethiazole is pharmacologically distinct from both the benzodiazepines and the barbiturates. Given alone its effects on respiration are slight and the therapeutic index high.