Enflurane (2-chloro-1,1,2,-trifluoroethyl-difluoromethyl ether) is a halogenated ether structural isomer of isoflurane. Developed by Ross Terrell in 1963, it was first used clinically in 1966. It was increasingly used for inhalational anesthesia during the 1970s and 1980s but is no longer in common use. Clinically, enflurane produces a dose-related depression of myocardial contractility with an associated decrease in myocardial oxygen consumption. Between 2% and 5% of the inhaled dose is oxidized in the liver, producing fluoride ions and difluoromethoxy-difluoroacetic acid. This is significantly higher than the metabolism of its structural isomer isoflurane. The exact mechanism of the action of general anesthetics has not been delineated. Enflurane acts as a positive allosteric modulator of the GABAA, glycine, and 5-HT3 receptors, and as a negative allosteric modulator of the AMPA, kainate, and NMDA receptors, as well as of nicotinic acetylcholine receptors.

Methaqualone is a depressant that modulates the activity of the GABA receptors in the brain and nervous system. It promotes relaxation, sleepiness and sometimes a feeling of euphoria. It causes a drop in blood pressure and slows the pulse rate. These properties are the reason why it was initially thought to be a useful sedative and anxiolytic. Common side effects of Methaqualone include dizziness, nausea, vomiting, diarrhea, abdominal cramps, fatigue, itching, rashes, sweating, dry mouth, tingling sensation in arms and legs, seizures and its depressant effects include reduced heart rate and respiration. The drug became banned in many countries and was withdrawn from many markets in the early 1980s.

Pregnenolone succinate is a synthetic pregnane steroid and an ester of pregnenolone which is described as a glucocorticoid and anti-inflammatory drug and has been patented and marketed as a topical medication in the form of a cream for the treatment of allergic, pruritic, and inflammatory dermatitis. In addition to its glucocorticoid effects, pregnenolone succinate has been found to act as a negative allosteric modulator of the GABAA receptor and a positive allosteric modulator of the NMDA receptor similarly to pregnenolone sulfate.

Halothane, USP is an inhalation anesthetic chemically designated 2-Bromo-2-chloro-1,1,1-trifluoroethane. Halothane, sold under the brand name Fluothane among others, is a general anesthetic. It can be used to start or maintain anesthesia. One of its benefits is that it does not increase the production of saliva which can be particularly useful in those who are difficult to intubate. Side effects include an irregular heartbeat, decreased effort to breath (respiratory depression), and liver problems. It should not be used in people with porphyria or a history of malignant hyperthermia either in themselves or their family members. It is unclear whether use during pregnancy is harmful to the baby, and it is not generally recommended for use during a cesarean section. Fluothane is no longer commercially available in the United States.

Glutethimide is a GABA agonist that was introduced by Ciba in 1954 as a safe alternative to barbiturates to treat insomnia. Before long, however, it had become clear that glutethimide was just as likely to cause addiction and caused similarly severe withdrawal symptoms. Glutethimide was discontinued in the US by manufacturers in 1993. Current production levels in the United States point to it only being used in small-scale research.

Ethchlorvynol is used to treat insomnia (trouble in sleeping). It developed by Pfizer in the 1950s. In the United States it was sold by Abbott Laboratories under the tradename Placidyl. Although the exact mechanism of action is unknown, ethchlorvynol appears to depress the central nervous system in a manner similar to that of barbiturates – by means of GABA-A receptors modulation. Moderate side effects are: Skin rash or hives; dizziness or faintness; unusual excitement, nervousness, or restlessness. It is addictive and after prolonged use can cause withdrawal symptoms including convulsions, hallucinations, and memory loss.

Methyprylon (brand name Noludar) is a sedative agent, which used to treat insomnia. But then the drug was replaced in the market by another drugs with less side effects. The precise mechanism of action is not known, but was made suggestion, that methyprylon increases the effects of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the brain.

Thiamylal is a barbiturate that is administered intravenously for the production of complete anesthesia of short duration, for the induction of general anesthesia, or for inducing a hypnotic state. Thiamylal, a barbiturate, is used in combination with acetaminophen or aspirin and caffeine for its sedative and relaxant effects in the treatment of tension headaches, migraines, and pain. Barbiturates act as nonselective depressants of the central nervous system (CNS), capable of producing all levels of CNS mood alteration from excitation to mild sedation, hypnosis, and deep coma. In sufficiently high therapeutic doses, barbiturates induce anesthesia. Thiamylal binds at a distinct binding site associated with a Cl- ionopore at the GABAA receptor, increasing the duration of time for which the Cl- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.

Talbutal is a short to intermediate-acting barbiturate, which had been used under brand name Latusate as a sedative and hypnotic, but then this usage was discontinued. It was found, that talbutal binds at a distinct binding site at the GABAA receptor, increasing the duration of time for which the Cl- ionopore is open. Thus, the post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.

Pregnenolone sulfate is an endogenous neurosteroid with excitatory effects in the brain, acting as a potent negative allosteric modulator of the GABAA receptor, a positive allosteric modulator of the NMDA receptor, and activator of transient receptor potential cation channel TRPM1 and TRPM3. In the model of schizophrenia, treatment with pregnenolone sulfate normalized the hyperlocomotion and stereotypic bouts, and rescued the PPI deficits of dopamine transporter knockout mice. Promnesic properties of pregnenolone sulfate were demonstrated in rat models of spatial memory performance.