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 The drug became banned in many countries and was withdrawn from many markets in the early 1980s.

HYDROXYPHENAMATE (LISTICA®) is a carbamate tranquilizer indicated for anxiety. It resembles meprobamate in its effect.

PHENAGLYCODOL is a propanediol-type tranquilizer used to treat a variety of nervous conditions and tensions including anxiety and depression. It can lead to gynecomastia and urinary steroid excretion in patients that are treated with the drug.

Benactyzine, an anticholinergic drug, had been used as an antidepressant in the treatment of depression and associated anxiety. It is no longer used in medicine due to its ineffectiveness but is widely used in scientific research. Benactyzine is a muscarinic antagonist which also inhibits the nicotinic acetylcholine receptor.

ECTYLUREA is used for the symptomatic treatment of tension and anxiety. It has no convulsant, analgesic or antispasmodic activity in animals. ECTYLUREA in therapeutic amounts has no effect on the autonomic nervous system. It also has no hypnotic effect unless given in a large dose.

Alverine is a smooth muscle relaxant used for the treatment irritable bowel syndrome. Alverine may increase calcium influx during action potentials due to inhibition of the inactivation of L-type calcium channels, but may also suppress evoked activity by inhibiting the sensitivity of contractile proteins to calcium.

AMOBARBITAL is a barbiturate derivative with hypnotic and sedative properties. In an in vitro study in rat thalamic slices amobarbital worked by activating GABAA receptors, which decreased input resistance, depressed burst and tonic firing, especially in ventrobasal and intralaminar neurons, while at the same time increasing burst duration and mean conductance at individual chloride channels; this increased both the amplitude and decay time of inhibitory postsynaptic currents. Adverse effects are mainly a consequence of dose-related CNS depression and the risk of dependence with continued use is high.

Mephobarbital us a barbiturate derivative used primary as an anticonvulsant, but also as a sedative and anxiolytic. Marketing of mephobarbital was discontinued in 2012.

Paraldehyde is the cyclic trimer of acetaldehyde molecules. It was introduced into clinical practice in the UK by the Italian physician Vincenzo Cervello in 1882. It is a central nervous system depressant and was soon found to be an effective anticonvulsant, hypnotic and sedative. It was included in some cough medicines as an expectorant (though there is no known mechanism for this function beyond the placebo effect). Paraldehyde also has been used in the treatment of alcoholism and in the treatment of nervous and mental conditions to calm or relax patients who are nervous or tense and to produce sleep. However, this medicine has generally been replaced by safer and more effective medicines for the treatment of alcoholism and in the treatment of nervous and mental conditions.

Chloral is a chlorinated aldehyde that found extensive use, beginning in the 1940s, as a precursor in the production of the insecticide DDT and, to a lesser extent, of other insecticides and pharmaceuticals. This use of chloral has declined steadily since the 1960s, especially in those countries where the use of DDT has been restricted. Chloral is readily converted to chloral hydrate in the presence of water. Chloral hydrate is used as a sedative before medical procedures and to reduce anxiety related to withdrawal from drugs. Wider exposure to chloral hydrate occurs at microgram-per-liter levels in drinking water and swimming pools as a result of chlorination. Chloral hydrate is a well-established aneuploidogenic agent that also has some mutagenic activity. In human cells in vitro, chloral hydrate induced aneuploidy, micronuclei and gene mutations. Chloral hydrate clearly induced micronuclei in Chinese hamster cells, whereas findings in mouse lymphoma cells were conflicting. Induction of somatic mutation (but not sex-linked mutation) by chloral hydrate was demonstrated in insects. Chloral hydrate is metabolized in vivo to trichloroethanol, which is responsible for its physiological and psychological effects. The metabolite of chloral hydrate exerts its pharmacological properties via enhancing the GABA receptor complex and therefore is similar in action to benzodiazepines, nonbenzodiazepines, and barbiturates. In clinical studies, oral chloral hydrate appears to have a lower sedation failure rate when compared with oral promethazine for children undergoing pediatric neurodiagnostic procedures. The sedation failure was similar for other comparisons such as oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam. When compared with intravenous pentobarbital and music therapy, oral chloral hydrate had a higher sedation failure rate. Compared to dexmedetomidine, chloral hydrate was associated with a higher risk of nausea and vomiting.