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.

Triethylene glycol is used in the vapor state as an air-sterilizing agent, toxic to bacteria, fungi and viruses in low concentrations in air. It is used in cosmetics as a fragrance ingredient and as a viscosity-decreasing agent. Commercially available triethylene glycol increased non-rapid eye movement sleep in mice in a dose-dependent manner. These results clearly demonstrated that triethylene glycol could potentially be useful for insomnia therapy. Triethylene glycol is used for occasional constipation and other conditions.

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.

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.

Clotiazepam is a compound of the benzodiazepine class. The drug was developed in Japan and approved for the treatment of insomnia, anxiety and before anesthesia. Clotiazepam was marketed worlwide under different names, however, currently it is available only in South America under the name Neuroval and presumably in Japan. Clotiazepam exerts its action by binding and activating GABA-A receptors.

a-Hydroxytriazolam is a major urinary and blood metabolite of the benzodiazepine, triazolam, a pharmaceutical used to treat severe insomnia. It is suitable for use in LC/MS or GC/MS applications for clinical toxicology, forensic analysis, urine drug testing, or pharmaceutical research. Triazolam is a triazolobenzodiazepine with hypnotic properties, advocated for use in acute or chronic insomnia, situational insomnia in hospitalised patients, and insomnia associated with other disease states. As triazolam has a relatively short half-life of about 2 to 3 hours in healthy subjects and has only 1 short acting active metabolite, alpha-hydroxytriazolam. a-Hydroxytriazolam is reported to have 50 to 100 % of the pharmacological activity of the parent compound. Triazolam (marketed in English-speaking countries under the brand names Apo-Triazo, Halcion, Hypam, and Trilam) is a benzodiazepine drug. It possesses pharmacological properties similar to that of other benzodiazepines, but it is generally only used as a sedative to treat severe insomnia. In addition to the hypnotic properties triazolam possesses, amnesic, anxiolytic, sedative, anticonvulsant and muscle relaxant properties are also present.

(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.

Valerian is on the FDA’s list of substances that are generally recognised to be safe (GRAS). The root oil and extracts may be used as spice or seasoning. Valerian is most commonly used for sleep disorders. The essential oil of valerian contains a variety of compounds including valerenic acid and its derivatives, hydroxyvalerenic acid, acetoxyvalerenic acid and valerenal.

Nimetazepam (Erimin) is an intermediate-acting hypnotic drug which is a benzodiazepine derivative. It was first synthesized in 1962 in Japan. It does possess hypnotic, anxiolytic, sedative, and skeletal muscle relaxant properties. Nimetazepam is also an anticonvulsant. It is sold in 5 mg tablets known as Erimin. It is generally prescribed for the treatment of short-term severe insomnia in patients who have difficulty falling asleep or maintaining sleep. Nimetazepam is currently a Schedule IV drug under the international Convention on Psychotropic Substances of 1971. In Singapore, nimetazepam is a class C drug under the Misuse of Drugs Act. In Hong Kong, nimetazepam is regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance. Nimetazepam can only be used legally by health professionals and for university research purposes.

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.