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Chloral hydrate is a geminal diol with the
formula In science, a formula is a concise way of expressing information symbolically, as in a mathematical formula or a ''chemical formula''. The informal use of the term ''formula'' in science refers to the general construct of a relationship betwe ...
. It is a colorless solid. It has limited use as a
sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but ...
and
hypnotic Hypnotic (from Greek ''Hypnos'', sleep), or soporific drugs, commonly known as sleeping pills, are a class of (and umbrella term for) psychoactive drugs whose primary function is to induce sleep (or surgical anesthesiaWhen used in anesthesia ...
pharmaceutical drug A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and ...
. It is also a useful laboratory chemical reagent and precursor. It is derived from chloral (trichloroacetaldehyde) by the addition of one equivalent of water.


History

Chloral hydrate was discovered in 1832 by
Justus von Liebig Justus Freiherr von Liebig (12 May 1803 – 20 April 1873) was a German scientist who made major contributions to agricultural and biological chemistry, and is considered one of the principal founders of organic chemistry. As a professor at th ...
in Gießen when a chlorination (
halogenation In chemistry, halogenation is a chemical reaction that entails the introduction of one or more halogens into a compound. Halide-containing compounds are pervasive, making this type of transformation important, e.g. in the production of polymers ...
) reaction was performed on
ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...
. Its
sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but ...
properties were observed by
Rudolf Buchheim Rudolf Buchheim (1 March 1820 – 25 December 1879) was a German pharmacologist born in Bautzen (Budziszyn). In 1845 he earned his doctorate from the University of Leipzig and shortly after became an associate professor of pharmacology, dieteti ...
in 1861, but described in detail and published only in 1869 by Oscar Liebreich; subsequently, because of its easy synthesis, its use became widespread. It was widely used for sedation in asylums and in general medical practice, and also became a popular drug of abuse in the late 19th century. One recreational user was the poet and illustrator Dante Gabriel Rossetti. Chloral hydrate is soluble in both water and ethanol, readily forming concentrated solutions. A solution of chloral hydrate in ethanol called "knockout drops" was used to prepare a Mickey Finn. More reputable uses of chloral hydrate include as a clearing agent for
chitin Chitin ( C8 H13 O5 N)n ( ) is a long-chain polymer of ''N''-acetylglucosamine, an amide derivative of glucose. Chitin is probably the second most abundant polysaccharide in nature (behind only cellulose); an estimated 1 billion tons of chit ...
and fibers and as a key ingredient in Hoyer's mounting medium, which is used to prepare permanent or semipermanent microscope slides of small organisms, histological sections, and
chromosome squash A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
es. Because of its status as a regulated substance, chloral hydrate can be difficult to obtain. This has led to chloral hydrate being replaced by alternative reagents in microscopy procedures. The compound can be crystalized in a variety of polymorphs.


Uses


Hypnotic

Chloral hydrate has not been approved by the FDA in the
United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country Continental United States, primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., ...
or the EMA in the
European Union The European Union (EU) is a supranational union, supranational political union, political and economic union of Member state of the European Union, member states that are located primarily in Europe, Europe. The union has a total area of ...
for any medical indication and is on the FDA list of unapproved drugs that are still prescribed by clinicians. Usage of the drug as a sedative or hypnotic may carry some risk given the lack of
clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...
s. However, chloral hydrate products, licensed for short-term management of severe insomnia, are available in the United Kingdom. Chloral hydrate was voluntarily removed from the market by all manufacturers in the United States in 2012. Prior to that, chloral hydrate may have been sold as a "legacy" or "grandfathered" drug;" that is, a drug that existed prior to the time certain FDA regulations took effect and therefore, some pharmaceutical companies have argued, has never required FDA approval. New drugs did not have to be approved for safety until Congress passed the Federal Food, Drug, and Cosmetic Act (the "FD&C Act") in 1938. Further, a new drug did not have to be proven effective until 1962, when Congress amended the Act. Manufacturers contend that such "legacy drugs," by virtue of the fact that they have been prescribed for decades, have gained a history for safety and efficacy. Chloral hydrate is used for the short-term treatment of
insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
and as a sedative before minor medical or dental treatment. It was largely displaced in the mid-20th century by
barbiturate Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential a ...
s and subsequently by benzodiazepines. It was also formerly used in veterinary medicine as a
general anesthetic General anaesthetics (or anesthetics, see spelling differences) are often defined as compounds that induce a loss of consciousness in humans or loss of righting reflex in animals. Clinical definitions are also extended to include an induced com ...
but is not considered acceptable for anesthesia or euthanasia of small animals due to adverse effects. It is also still used as a sedative prior to EEG procedures, as it is one of the few available sedatives that does not suppress epileptiform discharges. In therapeutic doses for insomnia, chloral hydrate is effective within 20 to 60 minutes. In humans it is
metabolized Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
within 7 hours into trichloroethanol and trichloroethanol glucuronide by erythrocytes and plasma esterases and into trichloroacetic acid in 4 to 5 days. It has a very narrow therapeutic window making this drug difficult to use. Higher doses can depress respiration and
blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure ...
.


In organic synthesis

Chloral hydrate is a starting point for the synthesis of other organic compounds. It is the starting material for the production of chloral, which is produced by the distillation of a mixture of chloral hydrate and
sulfuric acid Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid ( Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen and hydrogen, with the molecular fo ...
, which serves as the desiccant. Notably, it is used to synthesize isatin. In this synthesis, chloral hydrate reacts with
aniline Aniline is an organic compound with the formula C6 H5 NH2. Consisting of a phenyl group attached to an amino group, aniline is the simplest aromatic amine. It is an industrially significant commodity chemical, as well as a versatile starti ...
and hydroxylamine to give a condensation product which cyclicizes in
sulfuric acid Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid ( Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen and hydrogen, with the molecular fo ...
to give the target compound: : Moreover, chloral hydrate is used as a reagent for the deprotection of acetals, dithioacetals and tetrahydropyranyl ethers in organic solvents.


Botany and mycology


Hoyer's mounting medium

Chloral hydrate is also an ingredient used for Hoyer's solution, a
mounting medium A microscope slide is a thin flat piece of glass, typically 75 by 26 mm (3 by 1 inches) and about 1 mm thick, used to hold objects for examination under a microscope. Typically the object is mounted (secured) on the slide, and then ...
for microscopic observation of diverse plant types such as bryophytes,
fern A fern (Polypodiopsida or Polypodiophyta ) is a member of a group of vascular plants (plants with xylem and phloem) that reproduce via spores and have neither seeds nor flowers. The polypodiophytes include all living pteridophytes exce ...
s,
seed A seed is an embryonic plant enclosed in a protective outer covering, along with a food reserve. The formation of the seed is a part of the process of reproduction in seed plants, the spermatophytes, including the gymnosperm and angiosper ...
s, and small
arthropod Arthropods (, (gen. ποδός)) are invertebrate animals with an exoskeleton, a segmented body, and paired jointed appendages. Arthropods form the phylum Arthropoda. They are distinguished by their jointed limbs and cuticle made of chiti ...
s (especially
mite Mites are small arachnids (eight-legged arthropods). Mites span two large orders of arachnids, the Acariformes and the Parasitiformes, which were historically grouped together in the subclass Acari, but genetic analysis does not show clear e ...
s). Other ingredients may include gum arabic and
glycerol Glycerol (), also called glycerine in British English and glycerin in American English, is a simple triol compound. It is a colorless, odorless, viscous liquid that is sweet-tasting and non-toxic. The glycerol backbone is found in lipids known ...
. An advantage of this medium includes a high
refractive index In optics, the refractive index (or refraction index) of an optical medium is a dimensionless number that gives the indication of the light bending ability of that medium. The refractive index determines how much the path of light is bent, ...
and clearing (macerating) properties of small specimens (especially advantageous if specimens require observation with differential interference contrast microscopy).


Melzer's reagent

Chloral hydrate is an ingredient used to make Melzer's reagent, an aqueous solution that is used to identify certain species of
fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately fr ...
. The other ingredients are potassium iodide, and
iodine Iodine is a chemical element with the Symbol (chemistry), symbol I and atomic number 53. The heaviest of the stable halogens, it exists as a semi-lustrous, non-metallic solid at standard conditions that melts to form a deep violet liquid at , ...
. Whether tissue or spores react to this reagent is vital for the correct identification of some mushrooms.


Safety

Chloral hydrate was routinely administered in gram quantities. Prolonged exposure to the vapors is unhealthy, however, with a LD50 for 4-hour exposure of 440 mg/m3. Long-term use of chloral hydrate is associated with a rapid development of tolerance to its effects and possible addiction as well as adverse effects including rashes, gastric discomfort and severe kidney, heart, and liver failure. Acute overdosage is often characterized by
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of th ...
, vomiting, confusion, convulsions, slow and irregular breathing,
cardiac arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adult ...
, and
coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
. The plasma,
serum Serum may refer to: * Serum (blood), plasma from which the clotting proteins have been removed **Antiserum, blood serum with specific antibodies for passive immunity * Serous fluid, any clear bodily fluid *Truth serum, a drug that is likely to mak ...
or
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
concentrations of chloral hydrate and/or trichloroethanol, its major active metabolite, may be measured to confirm a diagnosis of poisoning in hospitalized patients or to aid in the forensic investigation of fatalities. Accidental overdosage of young children undergoing simple dental or surgical procedures has occurred. Hemodialysis has been used successfully to accelerate clearance of the drug in poisoning victims. It is listed as having a "conditional risk" of causing torsades de pointes.


Production

Chloral hydrate is produced from
chlorine Chlorine is a chemical element with the symbol Cl and atomic number 17. The second-lightest of the halogens, it appears between fluorine and bromine in the periodic table and its properties are mostly intermediate between them. Chlorine i ...
and
ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...
in acidic solution. :4 Cl2 + C2H5OH + H2O → Cl3CCH(OH)2 + 5 HCl In basic conditions the haloform reaction takes place and chloral hydrate is decomposed by
hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysi ...
to form
chloroform Chloroform, or trichloromethane, is an organic compound with formula C H Cl3 and a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to PTFE. It is also a precursor to various ...
.


Pharmacology


Pharmacodynamics

Chloral hydrate is metabolized ''
in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and p ...
'' to trichloroethanol, which is responsible for secondary physiological and psychological effects. Chloral hydrate is structurally and somewhat pharmacodynamically similar to ethchlorvynol, a pharmaceutical developed during the 1950's that was marketed as both a sedative and a hypnotic under the trade name Placidyl. In 1999, Abbott, the sole manufacturer of the drug in the United States at the time, decided to discontinue the product. After Abbott ceased production, the drug remained available for about a year. Despite the fact that it could have been manufactured generically, no other company in the United States chose to do so. The metabolite of chloral hydrate exerts its pharmacological properties via enhancing the
GABA receptor The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory compound in the mature vertebrate central nervous system. There are two classes of GABA receptors: GABAA and ...
complex and therefore is similar in action to benzodiazepines,
nonbenzodiazepines Nonbenzodiazepines (), sometimes referred to colloquially as Z-drugs (as many of their names begin with the letter "z"), are a class of psychoactive drugs that are very benzodiazepine-like in nature. They are used in the treatment of sleep problem ...
and
barbiturates Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential as we ...
. It can be moderately
addictive Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use oft ...
, as chronic use is known to cause dependency and withdrawal symptoms. The chemical can potentiate various
anticoagulant Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where t ...
s and is weakly mutagenic ''
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...
'' and ''in vivo''.


Legal status

In the United States, chloral hydrate is a schedule IV controlled substance and requires a physician's prescription. Its properties have sometimes led to its use as a date rape drug. The phrase, " slipping a mickey," originally referred specifically to adding chloral hydrate to a person's (alcoholic) drink without the person's knowledge.


History

Chloral hydrate was first synthesized by the chemist
Justus von Liebig Justus Freiherr von Liebig (12 May 1803 – 20 April 1873) was a German scientist who made major contributions to agricultural and biological chemistry, and is considered one of the principal founders of organic chemistry. As a professor at th ...
in 1832 at the University of Giessen. Through experimentation physiologist Claude Bernard clarified that the chloral hydrate was
hypnotic Hypnotic (from Greek ''Hypnos'', sleep), or soporific drugs, commonly known as sleeping pills, are a class of (and umbrella term for) psychoactive drugs whose primary function is to induce sleep (or surgical anesthesiaWhen used in anesthesia ...
as opposed to an
analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...
. It was the first of a long line of sedatives, most notably the
barbiturate Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential a ...
s, manufactured and marketed by the German pharmaceutical industry. Historically, chloral hydrate was utilized primarily as a psychiatric medication. In 1869, German physician and pharmacologist Oscar Liebreich began to promote its use to calm anxiety, especially when it caused insomnia. Chloral hydrate had certain advantages over
morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies ('' Papaver somniferum''). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. T ...
for this application, as it worked quickly without injection and had a consistent strength. It achieved wide use in both asylums and the homes of those socially refined enough to avoid asylums. Upper- and middle-class women, well-represented in the latter category, were particularly susceptible to chloral hydrate
addiction Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use o ...
. After the 1904 invention of barbital, the first of the
barbiturate Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential a ...
family, chloral hydrate began to disappear from use among those with means. It remained common in asylums and hospitals until the Second World War as it was quite cheap. Chloral hydrate had some other important advantages that kept it in use for five decades despite the existence of more advanced
barbiturate Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential a ...
s. It was the safest available sedative until the middle of the twentieth century, and thus was particularly favored for children. It also left patients much more refreshed after a deep sleep than more recently invented sedatives. Its frequency of use made it an early and regular feature in '' The Merck Manual''. Chloral hydrate was also a significant object of study in various early pharmacological experiments. In 1875, Claude Bernard tried to determine if chloral hydrate exerted its action through a metabolic conversion to
chloroform Chloroform, or trichloromethane, is an organic compound with formula C H Cl3 and a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to PTFE. It is also a precursor to various ...
. This was not only the first attempt to determine whether different drugs were converted to the same
metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...
in the body but also the first to measure the concentration of a particular pharmaceutical in the blood. The results were inconclusive. In 1899 and 1901
Hans Horst Meyer Hans Horst Meyer (17 March 1853 – 6 October 1939) was a German pharmacologist. He studied medicine and did research in pharmacology. The Meyer-Overton hypothesis on the mode of action on general anaesthetics is partially named after him. ...
and
Ernest Overton Charles Ernest Overton (1865–1933) was a British physiologist and biologist, now regarded as a pioneer of the theory of the cell membrane. In the last years of the 19th century Overton did experimental work, allowing the distinction to be draw ...
respectively made the major discovery that the general anaesthetic action of a drug was strongly correlated to its
lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids in ...
solubility In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution. The extent of the solubi ...
. However, chloral hydrate was quite polar but nonetheless a potent hypnotic. Overton was unable to explain this mystery. Thus, chloral hydrate remained one of the major and persistent exceptions to this breakthrough discovery in pharmacology. This anomaly was eventually resolved in 1948, when Claude Bernard's experiment was repeated. While chloral hydrate was converted to a different metabolite than chloroform, it was found that it was converted into the more lipophilic molecule 2,2,2-trichloroethanol. This metabolite fit much better with the Meyer–Overton correlation than chloral had. Prior to this, it had not been demonstrated that general anesthetics could undergo chemical changes to exert their action in the body. Finally, chloral hydrate was also the first hypnotic to be used intravenously as a general anesthetic. In 1871, Pierre-Cyprien Oré began experiments on animals, followed by humans. While a state of general anesthesia could be achieved, the technique never caught on because its administration was more complex and less safe than the oral administration of chloral hydrate, and less safe for intravenous use than later general anesthetics were found to be.


Society and culture

Chloral hydrate was used as one of the earliest synthetic drugs to treat
insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
. In 1912, Bayer introduced the drug phenobarbital under the brand name Luminal. In the 1930s, pentobarbital and secobarbital (better known by their original brand names Nembutal and Seconal, respectively) were synthesized. Chloral hydrate was still prescribed, although its predominance as a sedative and a hypnotic was largely eclipsed by barbiturates. In 1897, Bram Stoker's epistolary novel '' Dracula'', one of its characters, Doctor John Seward, recorded his use and his molecular formula in his
phonograph A phonograph, in its later forms also called a gramophone (as a trademark since 1887, as a generic name in the UK since 1910) or since the 1940s called a record player, or more recently a turntable, is a device for the mechanical and analogu ...
ic diary:
I cannot but think of Lucy, and how different things might have been. If I don't sleep at once, chloral, the modern Morpheus— C2HCl3O . H2O! I should be careful not to let it grow into a habit. No I shall take none to-night! I have thought of Lucy, and I shall not dishonor her by mixing the two.
In the conclusion of Edith Wharton's 1905 novel '' The House of Mirth'', Lily Bart, the novel's heroine, becomes addicted to chloral hydrate and overdoses on the substance:
She put out her hand and measured the soothing drops into a glass; but as she did so, she knew they would be powerless against the supernatural lucidity of her brain. She had long since raised the dose to its highest limit, but to-night she felt she must increase it. She knew she took a slight risk in doing so; she remembered the chemist's warning. If sleep came at all, it might be a sleep without waking.


Notable users

* King Chulalongkorn of
Thailand Thailand ( ), historically known as Siam () and officially the Kingdom of Thailand, is a country in Southeast Asia, located at the centre of the Indochinese Peninsula, spanning , with a population of almost 70 million. The country is b ...
(1853–1910) used the drug for a period after 1893 to relieve what may have been a mix of depression and unspecified illnesses. He is reported by his doctor to have been taking one bottle per day during July 1894 although this was reduced after this time. * Montgomery Clift (1920–1966) * André Gide (1869–1951) was given chloral hydrate as a boy for sleep problems by a physician named Lizart. Gide states in his autobiography '' If It Die...'' that "all my later weaknesses of will or memory I attribute to him." *
William James William James (January 11, 1842 – August 26, 1910) was an American philosopher, historian, and psychologist, and the first educator to offer a psychology course in the United States. James is considered to be a leading thinker of the lat ...
(1842–1910), psychologist and philosopher, used the drug for insomnia and sedation due to chronic neurosis. * The Jonestown mass murder-suicides in 1978 involved the communal drinking of
Flavor Aid Flavor Aid is a non-carbonated soft drink beverage made by The Jel Sert Company in West Chicago, Illinois. It was introduced in 1929. It is sold throughout the United States as an unsweetened, powdered concentrate drink mix, similar to Kool ...
poisoned with Valium, chloral hydrate,
cyanide Cyanide is a naturally occurring, rapidly acting, toxic chemical that can exist in many different forms. In chemistry, a cyanide () is a chemical compound that contains a functional group. This group, known as the cyano group, consists of ...
, and Phenergan. * Mary Todd Lincoln (1818–1882), wife of American president
Abraham Lincoln Abraham Lincoln ( ; February 12, 1809 – April 15, 1865) was an American lawyer, politician, and statesman who served as the 16th president of the United States from 1861 until his assassination in 1865. Lincoln led the nation throu ...
, became addicted in the years after her husband's death and was committed to an asylum. *
Marilyn Monroe Marilyn Monroe (; born Norma Jeane Mortenson; 1 June 1926 4 August 1962) was an American actress. Famous for playing comedic " blonde bombshell" characters, she became one of the most popular sex symbols of the 1950s and early 1960s, as wel ...
(1926–1962) died from an overdose of chloral hydrate and pentobarbital (Nembutal). *
Friedrich Nietzsche Friedrich Wilhelm Nietzsche (; or ; 15 October 1844 – 25 August 1900) was a German philosopher, prose poet, cultural critic, philologist, and composer whose work has exerted a profound influence on contemporary philosophy. He began his ...
(1844–1900) regularly used chloral hydrate in the years leading up to his nervous breakdown, according to Lou Salome and other associates. Whether the drug contributed to his insanity is a point of controversy. * Dante Gabriel Rossetti (1828–1882) became addicted to chloral, with whisky chasers, after the death of his wife Elizabeth Siddal from a
laudanum Laudanum is a tincture of opium containing approximately 10% powdered opium by weight (the equivalent of 1% morphine). Laudanum is prepared by dissolving extracts from the opium poppy (''Papaver somniferum Linnaeus'') in alcohol (ethanol). R ...
overdose in 1862. He had a mental breakdown in 1872. He lived out the last ten years of his life addicted to chloral and alcohol, in part to mask the pain of botched surgery to an enlarged testicle in 1877. * Oliver Sacks (1933–2015) abused chloral hydrate in 1965 as a depressed insomniac. He found himself taking fifteen times the usual dose of chloral hydrate every night before he eventually ran out, causing violent withdrawal symptoms. * Anna Nicole Smith (1967–2007) died of "
combined drug intoxication Combined drug intoxication (CDI), or multiple drug intake (MDI), is a cause of death by drug overdose from poly drug use, often implicated in polysubstance dependence. Deaths by combined drug intoxication are relatively rare (one in several mi ...
" with chloral hydrate as the "major component". *
John Tyndall John Tyndall FRS (; 2 August 1820 – 4 December 1893) was a prominent 19th-century Irish physicist. His scientific fame arose in the 1850s from his study of diamagnetism. Later he made discoveries in the realms of infrared radiation and the ...
(1820–1893), an Irish physicist, died of an accidental overdose of chloral administered by his wife. * Evelyn Waugh (1903–1966), insomniac for much of his adult life, for which "in later life ... he became so deleteriously dependent on chloral". Waugh's novel, ''
The Ordeal of Gilbert Pinfold ''The Ordeal of Gilbert Pinfold'' is a novel by the British writer Evelyn Waugh, first published in July 1957. It is Waugh's penultimate full-length work of fiction, which the author called his "mad book"—a largely autobiographical account ...
'', is largely a fictionalised account of an episode Waugh himself experienced as a result of excessive use of chloral in combination with bromide and alcohol. Waugh's friend and biographer Christopher Sykes observed that Waugh's description of D. G. Rossetti's demise under the effects of excessive use of chloral in his 1928 biography of the artist "is a fairly exact description of how augh's ownlife ended in 1966". *
Hank Williams Hank Williams (born Hiram Williams; September 17, 1923 – January 1, 1953) was an American singer, songwriter, and musician. Regarded as one of the most significant and influential American singers and songwriters of the 20th century, he reco ...
(1923–1953) died from a combination of chloral hydrate,
morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies ('' Papaver somniferum''). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. T ...
and
whiskey Whisky or whiskey is a type of distilled alcoholic beverage made from fermented grain mash. Various grains (which may be malted) are used for different varieties, including barley, corn, rye, and wheat. Whisky is typically aged in wooden ...
.


Environmental

It is, together with
chloroform Chloroform, or trichloromethane, is an organic compound with formula C H Cl3 and a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to PTFE. It is also a precursor to various ...
, a minor side-product of the chlorination of water when organic residues such as
humic acids Humic substances (HS) are organic compounds that are important components of humus, the major organic fraction of soil, peat, and coal (and also a constituent of many upland streams, dystrophic lakes, and ocean water). For a long era in the 19th a ...
are present. It has been detected in drinking water at concentrations of up to 100 micrograms per litre (µg/L) but concentrations are normally found to be below 10 µg/L. Levels are generally found to be higher in
surface water Surface water is water located on top of land forming terrestrial (inland) waterbodies, and may also be referred to as ''blue water'', opposed to the seawater and waterbodies like the ocean. The vast majority of surface water is produced by pre ...
than in ground water.


See also

*
Chlorobutanol Chlorobutanol (trichloro-2-methyl-2-propanol) is a preservative, sedative, hypnotic and weak local anesthetic similar in nature to chloral hydrate. It has antibacterial and antifungal properties. Chlorobutanol is typically used at a concentration ...
* Disulfiram-like drug * Trichloroethanol


References

Notes Sources *


External links

* {{DEFAULTSORT:Chloral Hydrate Acetaldehyde dehydrogenase inhibitors Aldehydes GABAA receptor positive allosteric modulators Glycine receptor agonists Hydrates Hypnotics Sedatives Organochlorides Prodrugs Trichloromethyl compounds Geminal diols