Paraldehyde
Encyclopedia
Paraldehyde is the cyclic trimer
of acetaldehyde
molecules. Formally, it is a derivative of 1,3,5-trioxane
. The corresponding tetramer is metaldehyde
. A colourless liquid, it is sparingly soluble in water and highly soluble in alcohol. Paraldehyde slowly oxidizes in air, turning brown and producing an odour of acetic acid
. It quickly reacts with most plastics and rubber.
Paraldehyde was first synthesized in 1829 by Wildenbusch. It has uses in industry and medicine.
:
Since paraldehyde has better handling characteristics, it may be used indirectly or directly as a synthetic equivalent of anhydrous acetaldehyde (b.p. 20 °C). For example, it is used as-is in the synthesis of bromal (tribromoacetaldehyde):
It is a CNS
depressant
and was soon found to be an effective anticonvulsant
, hypnotic
and sedative
. It was included in some cough medicine
s as an expectorant (though there is no known mechanism for this function beyond the placebo effect
).
Paraldehyde was the last injection given to Edith Alice Morrell
in 1950 by the suspected serial killer John Bodkin Adams
. He was tried for her murder but acquitted.
but has been replaced by other drugs in this regard. It is one of the safest hypnotics and was regularly given at bedtime in psychiatric hospital
s and geriatric
wards up to the 1960s. Up to 30% of the dose is excreted via the lungs (the rest via the liver). This contributes to a strong unpleasant odour on the breath.
s.
Today, paraldehyde is sometimes used to treat status epilepticus
. Unlike diazepam
and other benzodiazepines, it does not suppress breathing at therapeutic doses and so is safer when no resuscitation facilities exist or when the patient's breathing is already compromised. This makes it a useful emergency medication for parents and other caretakers of children with epilepsy. Since the dose margin between the anticonvulsant and hypnotic effect is small, paraldehyde treatment usually results in sleep.
Generic paraldehyde is available in 5ml sealed glass ampoules. Production in the US has been discontinued, but it was previously marketed as Paral.
Paraldehyde has been given orally, rectally, intravenously and by intramuscular injection. It reacts with rubber and plastic which limits the time it may safely be kept in contact with some syringes or tubing before administration.
manufacture, as a preservative
, and in other processes as a solvent
.
It has been used in the generation of aldehyde fuchsin.
Trimer (chemistry)
In chemistry, a trimer is a product derived from three identical precursors. Trimers are typically cyclic. Chemical compounds that often trimerise are aliphatic isocyanates and cyanic acids. Often, trimerization competes with polymerization....
of acetaldehyde
Acetaldehyde
Acetaldehyde is an organic chemical compound with the formula CH3CHO or MeCHO. It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale industrially. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants as part...
molecules. Formally, it is a derivative of 1,3,5-trioxane
1,3,5-Trioxane
1,3,5-Trioxane, sometimes also called trioxin, is a chemical compound with molecular formula C3H6O3. It is a stable cyclic trimer of formaldehyde, and one of the two trioxane isomers; its molecular backbone consists of a six membered ring with three carbon atoms alternating with three oxygen...
. The corresponding tetramer is metaldehyde
Metaldehyde
Metaldehyde is an organic compound with the formula 4. It is commonly used as a pesticide against slugs, snails, and other gastropods. It is the cyclic tetramer of acetaldehyde.-Production and properties:...
. A colourless liquid, it is sparingly soluble in water and highly soluble in alcohol. Paraldehyde slowly oxidizes in air, turning brown and producing an odour of acetic acid
Acetic acid
Acetic acid is an organic compound with the chemical formula CH3CO2H . It is a colourless liquid that when undiluted is also called glacial acetic acid. Acetic acid is the main component of vinegar , and has a distinctive sour taste and pungent smell...
. It quickly reacts with most plastics and rubber.
Paraldehyde was first synthesized in 1829 by Wildenbusch. It has uses in industry and medicine.
Stereochemistry
Theoretically four stereoisomeric structures are possible. The structures (1) and (2) are known as cis- and trans-paraldehyde. The structures (3) and (4) don't exist for steric reasons.Reactions
Heated with catalytic amounts of acid, it depolymerizes back to acetaldehydeAcetaldehyde
Acetaldehyde is an organic chemical compound with the formula CH3CHO or MeCHO. It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale industrially. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants as part...
:
- C6H12O3 → 3CH3CHO
Since paraldehyde has better handling characteristics, it may be used indirectly or directly as a synthetic equivalent of anhydrous acetaldehyde (b.p. 20 °C). For example, it is used as-is in the synthesis of bromal (tribromoacetaldehyde):
- C6H12O3 + 9 Br2 → 3 CBr3CHO + 9 HBr
Medical applications
Paraldehyde was introduced into clinical practice in the UK by the Italian physician Vincenzo Cervello in 1882.It is a CNS
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
depressant
Depressant
A depressant, or central depressant, is a drug or endogenous compound that depresses the function or activity of a specific part of the brain...
and was soon found to be an effective anticonvulsant
Anticonvulsant
The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
, hypnotic
Hypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
and sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
. It was included in some cough medicine
Cough medicine
A cough medicine is a medicinal drug used in an attempt to treat coughing and related conditions. For dry coughs, treatment with cough suppressants may be attempted to suppress the body's urge to cough...
s as an expectorant (though there is no known mechanism for this function beyond the placebo effect
Placebo effect
Placebo effect may refer to:* Placebo effect, the tendency of any medication or treatment, even an inert or ineffective one, to exhibit results simply because the recipient believes that it will work...
).
Paraldehyde was the last injection given to Edith Alice Morrell
Edith Alice Morrell
Edith Alice Morrell , was a resident of Eastbourne and patient of the suspected serial killer John Bodkin Adams. He was tried for her murder in 1957 but acquitted...
in 1950 by the suspected serial killer John Bodkin Adams
John Bodkin Adams
John Bodkin Adams was an Irish-born British general practitioner, convicted fraudster and suspected serial killer. Between the years 1946 and 1956, more than 160 of his patients died in suspicious circumstances. Of these, 132 left him money or items in their will. He was tried and acquitted for...
. He was tried for her murder but acquitted.
As a hypnotic/sedative
It was commonly used to induce sleep in sufferers from delirium tremensDelirium tremens
Delirium tremens is an acute episode of delirium that is usually caused by withdrawal from alcohol, first described in 1813...
but has been replaced by other drugs in this regard. It is one of the safest hypnotics and was regularly given at bedtime in psychiatric hospital
Psychiatric hospital
Psychiatric hospitals, also known as mental hospitals, are hospitals specializing in the treatment of serious mental disorders. Psychiatric hospitals vary widely in their size and grading. Some hospitals may specialise only in short-term or outpatient therapy for low-risk patients...
s and geriatric
Geriatrics
Geriatrics is a sub-specialty of internal medicine and family medicine that focuses on health care of elderly people. It aims to promote health by preventing and treating diseases and disabilities in older adults. There is no set age at which patients may be under the care of a geriatrician, or...
wards up to the 1960s. Up to 30% of the dose is excreted via the lungs (the rest via the liver). This contributes to a strong unpleasant odour on the breath.
As anti-seizure
It has been used in the treatment of convulsionConvulsion
A convulsion is a medical condition where body muscles contract and relax rapidly and repeatedly, resulting in an uncontrolled shaking of the body. Because a convulsion is often a symptom of an epileptic seizure, the term convulsion is sometimes used as a synonym for seizure...
s.
Today, paraldehyde is sometimes used to treat status epilepticus
Status epilepticus
Status epilepticus is a life-threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but traditionally it is defined as one continuous unremitting seizure lasting longer than 5 minutes, or recurrent seizures without regaining consciousness between seizures...
. Unlike diazepam
Diazepam
Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...
and other benzodiazepines, it does not suppress breathing at therapeutic doses and so is safer when no resuscitation facilities exist or when the patient's breathing is already compromised. This makes it a useful emergency medication for parents and other caretakers of children with epilepsy. Since the dose margin between the anticonvulsant and hypnotic effect is small, paraldehyde treatment usually results in sleep.
Administration
Paraldehyde has been given orally, rectally, intravenously and by intramuscular injection. It reacts with rubber and plastic which limits the time it may safely be kept in contact with some syringes or tubing before administration.
- Injection. Intramuscular injection can be very painful and lead to sterile abscesses, nerve damage, and tissue necrosis. Intravenous administration can lead to pulmonary edemaPulmonary edemaPulmonary edema , or oedema , is fluid accumulation in the air spaces and parenchyma of the lungs. It leads to impaired gas exchange and may cause respiratory failure...
, circulatory collapseCirculatory collapseA circulatory collapse is defined as a general or specific failure of the circulation, either cardiac or peripheral in nature. A common cause of this could be shock or trauma from injury or surgery...
and other complications.
- Oral. Paraldehyde has a hot burning taste and can upset the stomach. It is often mixed with milk or fruit juice in a glass cup and stirred with a metal spoon.
- Rectal. It may be mixed 1 part paraldehyde with 9 parts saline or, alternatively, with an equal mixture of peanutPeanut oilPeanut oil is an organic material oil derived from peanuts, noted to have the aroma and taste of its parent legume....
or olive oilOlive oilOlive oil is an oil obtained from the olive , a traditional tree crop of the Mediterranean Basin. It is commonly used in cooking, cosmetics, pharmaceuticals, and soaps and as a fuel for traditional oil lamps...
.
Industrial applications
Paraldehyde is used in resinResin
Resin in the most specific use of the term is a hydrocarbon secretion of many plants, particularly coniferous trees. Resins are valued for their chemical properties and associated uses, such as the production of varnishes, adhesives, and food glazing agents; as an important source of raw materials...
manufacture, as a preservative
Preservative
A preservative is a naturally occurring or synthetically produced substance that is added to products such as foods, pharmaceuticals, paints, biological samples, wood, etc. to prevent decomposition by microbial growth or by undesirable chemical changes....
, and in other processes as a solvent
Solvent
A solvent is a liquid, solid, or gas that dissolves another solid, liquid, or gaseous solute, resulting in a solution that is soluble in a certain volume of solvent at a specified temperature...
.
It has been used in the generation of aldehyde fuchsin.