Chloral hydrate was first synthesized in 1832 by Justus von Liebig and was the first synthetic central nervous system (CNS) depressant. It was used to treat delirium tremens, insomnia, and anxiety, although it is considered an unapproved drug by the US Food and Drug Administration. Initially considered to be a safer alternative to opium, it was noted to produce rapid unconsciousness when combined with ethanol. Physical dependence can occur with chronic use.

Uses

Chloral hydrate is used as a sedative hypnotic, more commonly in pediatrics. With the advent of newer sedative hypnotics, its use has significantly decreased. It is also a drug of abuse, particularly in combination with ethanol to produce an amnestic effect in an individual who ingests it unknowingly.

Environmental Fate

Chloral hydrate has been detected at 5 mg l^-1 in the US drinking water supply. Although chloral hydrate does not exist naturally, it can be produced as a by-product of chlorination of water at water treatment facilities, specifically in exposed water with high amounts of humic and fulvic substances.

Mechanism

Chloral hydrate is a CNS depressant, but its mechanism of action is not well known. Coingestion with ethanol produces enhanced effects by several mechanisms. First, ethanol competes for alcohol and aldehyde dehydrogenase, which then prolongs the half-life of ethanol. The metabolism of ethanol generates the reduced form of NADH, which is a cofactor for the metabolism of chloral hydrate to its active metabolite trichloroethanol. Finally, ethanol inhibits the conjugation of trichloroethanol to its inactive form urochloralic acid. This results in enhanced CNS depression.