Early clinical neurochemistry of CNS-active drugs. Chloral hydrate

Chloral hydrate was introduced into therapeutics more than 120 years ago, and soon became popular as a somnifacient. It is the first synthetic CNS depressant. Its metabolite, urochloralic acid, was detected early. Studies of the biochemical pharmacology of chloral hydrate have engaged the attention of many investigators in succeeding years. Its mode of action in producing sleep was initially attributed to the possibility that it gives rise to chloroform in vivo. Although this hypothesis did not stand up to scientific scrutiny, it led to efforts to establish how chloral hydrate brings about its action. This seems to be through its reduced metabolite, trichloroethanol. The precise mode of action on the nervous system remains to be worked out.