Chloral hydrate
Discover related
2 sources
Collated from TripSit, Pharmacology. Where sources differ (e.g. dosing), Compare shows them side by side.
Also known as chloral-hydrate, aquachloral, somnosTS
Chloral Hydrate, a sedative drug discovered in 1832 with a history of recreational use going back to the 19th century. Sometimes prescribed for extreme insomnia. For such an old drug, relatively little is known about its long-term term effects on the body. Produces intoxication comparable to alcohol or benzodiazepines.TS
Oral
Route dataTripSit
| Threshold | Light | Common | Strong | Heavy |
|---|---|---|---|---|
| — | — | 200–500 mg | 500–1000 mg | —+ |
| Onset | 20–60 minutes |
|---|---|
| Total | 5–10 hours |
| After-effects | 2–6 hours |
Mechanism of actionPH
Chloral hydrate has CNS depressant effects similar to those of paraldehyde and the barbiturates. The mechanism of action of the drug is not completely known. The CNS depressant effect of chloral hydrate is believed to result mainly from its metabolite, trichloroethanol, although some animal studies have indicated that the rapid onset of sedation and hypnosis that chloral hydrate produces may be due to chloral hydrate itself and that the prolonged duration of action may be due to trichloroethanol.
Pharmacokinetics
Half-lifePH
The plasma half-life of trichloroethanol, the active metabolite, is about 7 to 10 hours.
The average half-life of trichloroethanol glucuronide was 6.7 hr. The average plasma half-life for chloral hydrate metabolites was 8.2 hr; the half-life of the third chloral hydrate metabolite, trichloroacetic acid, was about four days, as it binds extensively to plasma proteins.
The plasma half-life for therapeutic doses of chloral hydrate is 4 to 5 min, whereas for trichloroethanol /a metabolite/ is 8 to 12 hr and for trichloroacetic acid /a metabolite/, 67 hr.
This study was designed to characterize the kinetics of chloral hydrate (CH) metabolism, and the formation and elimination of trichloroacetate (TCA), dichloroacetate (DCA), trichloroethanol (TCOH), and trichloroethanol glucuronide (TCOG) in male B6C3F1 mice. Mice were dosed with 67.8, 678, and 2034 umol/kg of CH through the tail vein. ... After intravenous administration, CH rapidly disappeared from blood with a terminal half-life ranging from 5 to 24 min. ... The terminal half-lives of TCOH and TCOG were similar, ranging from 0.2 to 0.7 hr. ...
AbsorptionPH
Rapidly absorbed in the GI tract following oral or rectal administration. Chloral hydrate and its active metabolite, trichloroethanol, have been detected in CSF, umbilical cord blood, fetal blood, and amniotic fluid.
Trichloroethanol, trichloroethanol glucuronide, and trichloroacetic acid are excreted in the urine. Some trichloroethanol glucuronide may be secreted into bile and excreted in the feces.
Following therapeutic doses of chloral hydrate, only small, clinically insignificant amounts of the active metabolite are distributed into milk.
Chloral hydrate is rapidly absorbed from the GI tract following oral or rectal administration. Plasma concentrations of chloral hydrate (or the major metabolite, trichloroethanol) required for sedative or hypnotic effects are unknown. Following administration of a single chloral hydrate dose of 15 mg/kg, peak plasma concentrations of trichloroethanol ranged from 7-10 ug/mL in one study.
After oral administration, chloral hydrate is rapidly absorbed from the gastrointestinal tract. Peak levels of trichloroethanol and trichloroethanol glucuronide were reached within 20- 60 min after oral administration of aqueous solutions.
The volume of distribution of chloral hydrate is 0.6 L/kg.
MetabolismPH
Metabolized by the liver and erythrocytes to form trichloroethanol, an active metabolite. This reaction is catalyzed by alcohol dehydrogenase and other enzymes. Oxidation of chloral hydrate and trichloroethanol to trichloroacetic acid in the liver and kidneys also occurs to a lesser extent. Trichloroethanol also undergoes glucuronidation to produce an inactive metabolism.
/Chloral hydrate/ biotransformation to trichloroethanol must be rapid, since no parent compound could be detected in even the first samples taken 10 min after administration of 15 mg/kg bw to volunteers.
Chloral hydrate is metabolized by the liver and erythrocytes to form trichloroethanol (an active metabolite). The reduction of chloral hydrate to trichloroethanol (the major metabolite) is catalyzed by alcohol dehydrogenase and other enzymes. ... A small but variable amount of chloral hydrate and a larger portion of trichloroethanol are oxidized to trichloroacetic acid (an inactive metabolite), mainly in the liver and kidneys. Trichloroethanol may also be conjugated with glucuronic acid to form trichloroethanol glucuronide (urochloralic acid), an inactive metabolite. ... The quantities of metabolites excreted in the urine appear to be quite variable not only between different individuals but may even vary in the same individual on different days.
In mammalian species, chloral hydrate is rapidly reduced to trichloroethanol, the metabolite that appears to be responsible for the hypnotic properties of the drug. ... In rodents, a slightly different metabolic pattern is seen, as chloral hydrate is oxidized directly to trichloroacetic acid, and the oxidative pathway from trichloroethanol to trichloroacetate that is observed in humans seems to be absent.
As < 50% of an administered dose of chloral hydrate was recovered as metabolites in urine, yet unknown biotransformation reactions may exist for chloral hydrate in humans.
For more Metabolism/Metabolites (Complete) data for CHLORAL HYDRATE (10 total), please visit the HSDB record page.
Plan a dose of Chloral hydrate
Loading the fact-sheet…
Logging a dose needs somewhere to keep it. Start a free session — no signup; it and everything in it expire in 7 days.
External links
Fact-sheets from PsychonautWiki. Harm-reduction reference only — not medical advice.