Vinylbital is a barbiturate derivative. It was introduced into therapy in 1963 and used as a sedative and in the treatment of insomnia.

Niaprazine is a potent and selective antagonist of 5-HT2A and alpha-1 adrenergic receptors. It was used for the treatment of sleep disturbances in children and was investigated for the treatment of sleep disorders in patients with attention-deficit hyperactivity disorder and autistic disorder.

Apronalide is an acyclic analog of barbiturates. It was used under tradename "Sedormid" as a sedative an hypnotic agent. In 1934 it was discovered that the drug causes thrombocytopenic purpura. Apronalide is still marketed in Japan, where it is used in combination with caffeine and ibuprofen for the treatment of headache.

Valnoctamide is a valproic acid derivative associated with a decreased risk for congenital abnormalities and developed by Beersheva Mental Health Center for treatment mania. Valnoctamide has been marketed as an anxiolytic and sedative in several European countries (as Nirvanil), including Italy, Holland, and Switzerland, until the year 2000 but was not actively promoted as an anticonvulsant. It was marketed in the U.S. as Axiquel by McNeil Laboratories in the 1970s. In mice, valnoctamide has been shown to be distinctly less teratogenic than valproic acid. Injection of 3 mkmol ⁄ kg at day 8 of gestation produced only 1% exencephaly (as compared to 0–1% in control mice and 53% in valproate-treated mice). Embryolethality rates showed similar results: 52% with valproate versus 5% in the controls and 2% with valnoctamide. Valnoctamide's patent is expired, and it is not the property of any major pharmaceutical company. Valnoctamide has potential as a therapy in epilepsy including status epilepticus (SE) and neuropathic pain and is currently being developed for the treatment of mania and Schizoaffective Disorder. In clinical trials, Valnoctamide was well tolerated but lacked efficacy in the treatment of symptoms in patients with acute mania.

Chlorhexadol (or Chloralodol), a hypnotic compound which is included in the list of Schedule III drugs of the United States Controlled Substances Act.

Doxefazepam (marketed under brand name Doxans) is a benzodiazepine derivative with putative hypnotic, anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. The potency of action was estimated to be equivalent to diazepam in animal models, and in man, the compound proved to be CNS active in a placebo-controlled study, in which systematic modifications of the background EEG signal were detected after acute administration to awake volunteers. Doxefazepam (10 mg) reduced the number of intermediate awakenings and the shifts between distinct sleep phases; single 20- or 40-mg doses or a 2-week administration of 10 mg doxefazepam increased significantly the total sleep duration and the percent duration of phase 2 and the synchronized sleep and decreased the percent duration of phase 1 and of the intermediate awakenings.

Loprazolam is a hypnotic drug which stimulates GABA-A receptors. Due to its hypnotic activity the drug is used to treat short-term sleep disordes.

Chloral hydrate was discovered in 1832, and was used as a sedative in late 19th century. Chloral hydrate has not been approved by the FDA or the EMA, and is on the list of unapproved drugs that are prescribed for postoperative pain control, sedation and to prevent alcohol withdrawal and reduce anxiety associated with withdrawal of opiates or barbiturates. Mechanism of action of chloral hydrate is not known. It is generally believed that the central depressant effects are due to the principal pharmacologically active metabolite trichloroethanol, which has a plasma half- life of 8 to 10 hours, and acts by potentiating GABA-activated Cl currents.

Lormetazepam (or methyl-lorazepam), possesses hypnotic, anxiolytic, sedative and skeletal muscle relaxant properties. Lormetazepam is not approved for sale in the United States or Canada, though it is licensed in the Netherlands as 1 and 2 mg tablets, under the brand names Loramet and Noctamid and as generic, available from several different manufacturers. Lormetazepam is a short-acting benzodiazepine and is sometimes used in patients who have difficulty in maintaining sleep or falling asleep. Lormetazepam binds to the benzodiazepine receptor which in turn enhances the effect of the GABAA receptor producing its therapeutic effects as well as adverse effects. Lormetazepam appears to be more selective in the type of benzodiazepine receptor it binds to showing a higher affinity for the omega 1 receptor which is responsible for sedation. Changes in electroencephalography can therefore be used to measure the sedative sleep promoting properties of lormetazepam.

Bromisoval (INN; aka bromvalerylurea) is a hypnotic and sedative compound of the bromoureide group discovered by Knoll in 1907 and patented in 1909. It is marketed over the counter in Asia under various trade names (such as Brovarin) usually in combination with non-steroidal anti-inflammatory drugs. Chronic use of bromisoval has been associated with bromine poisoning. Bromovisal can be prepared by bromination of isovaleric acid by the Hell-Volhard-Zelinsky reaction followed by reaction with urea. Bromvalerylurea (BU) can suppress expression of many kinds of pro- and anti-inflammatory mediators in LPS- or interferon-γ activated alveolar and peritoneal macrophages. Bromisoval was found to ameliorate sepsis in rats. It also prevents elevated serum-IL-6 level as well as IL-6 mRNA expression in septic rats. Bromisoval was also found useful for inflammatory skin disorders. The compound is able to suppress the TLR ligands-induced proinflammatory response similar to the steroid DEX without the side effects often associated with the steroid usage.