Sodium thiopental, better known as
Sodium Pentothal (a
trademarkA trademark, trade mark, or trade-mark is a distinctive sign or indicator used by an individual, business organization, or other legal entity to identify that the products or services to consumers with which the trademark appears originate from a unique source, and to distinguish its products or...
of
Abbott LaboratoriesAbbott Laboratories is an American-based global, diversified pharmaceuticals and health care products company. It has 90,000 employees and operates in over 130 countries. The company headquarters are in Abbott Park, North Chicago, Illinois. The company was founded by Chicago physician, Dr....
),
thiopental,
thiopentone sodium, or
Trapanal (also a trademark), is a rapid-onset short-acting
barbiturateBarbiturates are drugs that act as central nervous system depressants, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia. They are also effective as anxiolytics, as hypnotics, and as anticonvulsants...
general anaestheticA general anaesthetic is a drug that brings about a reversible loss of consciousness. These drugs are generally administered by an anaesthesia provider to induce or maintain general anaesthesia to facilitate surgery...
. Thiopental is a core medicine in the
World Health OrganizationThe World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
's "Essential Drugs List", which is a list of minimum medical needs for a basic healthcare system. It is also usually the first of three drugs administered during most
lethal injectionLethal injection is the practice of injecting a person with a fatal dose of drugs for the express purpose of causing the immediate death of the subject. The main application for this procedure is capital punishment, but the term may also be applied in a broad sense to euthanasia and suicide...
s in the United States.
Barbiturates
Barbiturates are a class of drugs that act on the
GABAA receptorThe GABAA receptor is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid , the major inhibitory neurotransmitter in the central nervous system. Upon activation, the GABAA receptor selectively conducts Cl- through its pore, resulting in...
in the brain and spinal cord. The GABA
A receptor is an inhibitory channel that decreases neuronal activity, and barbiturates enhance the inhibitory action of the GABA
A receptor. Barbiturates,
benzodiazepineA benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
s, and
alcoholIn chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
all bind to the GABA
A receptor. Barbiturates that act on the barbiturate binding site of the GABA
A receptor directly gate the chloride ion channel of the GABA
A receptor, whereas benzodiazepines acting on the benzodiazepine site on the GABA
A receptor increase the opening frequency of the chloride ion channel. This explains why overdoses of barbiturates may be lethal whereas overdoses of benzodiazepines alone are typically not lethal. Another explanation is that barbiturates can activate GABA receptors in the absence of the GABA molecule, whereas benzodiazepines need GABA to be present to have an effect: this may explain the more widespread effects of barbiturates in the central nervous system. Barbiturates have anesthetic,
sedativeA sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
,
anxiolyticAn anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
,
anticonvulsantThe 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...
and
hypnoticHypnotic 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...
properties. Barbiturates do not have
analgesicAn analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
effects.
Further, barbiturates are relatively "promiscuous" (i.e. non-selective) compounds that bind to an entire superfamily of ligand-gated ion channels, of which the GABA
A receptor channel is only one of several representatives. This superfamily of ion channels includes the neuronal nACHR channel, the 5HT3R channel, the GlyR channel and others. Surprisingly, while GABA
A receptor currents are increased by barbiturates (and other general anaesthetics), ligand-gated ion channels that are predominantly permeable for cationic ions are blocked by these compounds. For example, neuronal nACHR channels are blocked by clinically relevant anaesthetic concentrations of both thiopental and pentobarbital. Such findings implicate (non-GABA-ergic) ligand-gated ion channels, e.g. the neuronal nAChR channel, in mediating some of the (side) effects of barbiturates.
Anesthesia
Thiopental is an ultra-short-acting barbiturate and has been used commonly in the induction phase of
general anesthesiaGeneral anaesthesia is a state of unconsciousness and loss of protective reflexes resulting from the administration of one or more general anaesthetic agents...
. Its use in the United States and elsewhere has been largely replaced with that of
propofolPropofol is a short-acting, intravenously administered hypnotic agent. Its uses include the induction and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. Propofol is also commonly used in veterinary medicine...
. Following
intravenousIntravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
injectionAn injection is an infusion method of putting fluid into the body, usually with a hollow needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body...
the drug rapidly reaches the brain and causes unconsciousness within 30–45 seconds. At one minute, the drug attains a peak concentration of about 60% of the total dose in the brain. Thereafter, the drug distributes to the rest of the body and in about 5–10 minutes the concentration is low enough in the brain such that consciousness returns.
A normal dose of thiopental (usually 4–6 mg/kg) given to a pregnant woman for operative delivery (caesarian section) rapidly makes her unconscious, but the baby in her
uterusThe uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
remains conscious. However, larger or repeated doses can depress the baby.
Thiopental is not used to maintain anesthesia in surgical procedures because, in infusion, it displays zero-order elimination kinetics, leading to a long period before consciousness is regained. Instead, anesthesia is usually maintained with an
inhaled anestheticAn inhalational anaesthetic is a chemical compound possessing general anaesthetic properties that can be delivered via inhalation. They are administered by anaesthetists through an anaesthesia mask, laryngeal mask airway or tracheal tube connected to some type of anaesthetic vaporiser and an...
(gas) agent. Inhaled anesthetics are eliminated relatively quickly, so that stopping the inhaled anesthetic will allow rapid return of consciousness. Thiopental would have to be given in large amounts to maintain an anesthetic plane, and because of its 11.5–26 hour
half-lifeThe biological half-life or elimination half-life of a substance is the time it takes for a substance to lose half of its pharmacologic, physiologic, or radiologic activity, as per the MeSH definition...
, consciousness would take a long time to return.
In
veterinary medicineVeterinary Medicine is the branch of science that deals with the prevention, diagnosis and treatment of disease, disorder and injury in non-human animals...
, thiopental is used to induce
anesthesia in animalsVeterinary anesthesia is anesthesia performed on animals by a veterinarian. Anesthesia is used for a wider range of circumstances in animals than in people, due to animals' unwillingness to cooperate with certain diagnostic or therapeutic procedures...
. Since thiopental is redistributed to fat, certain breeds of dogs – primarily the sight hounds – can have prolonged recoveries from thiopental due to their lack of body fat and their lean body mass. Thiopental is always administered intravenously, as it can be fairly irritating; severe tissue necrosis and sloughing can occur if it is injected incorrectly into the tissue around a vein.
Medically induced coma
In addition to anesthesia induction, thiopental was historically used to induce medical
comaIn medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
s. It has now been superseded by drugs such as
propofolPropofol is a short-acting, intravenously administered hypnotic agent. Its uses include the induction and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. Propofol is also commonly used in veterinary medicine...
.
Thiopental has a long Context Sensitive Half Time (CSHT), meaning infusions saturate peripheral compartments (fat, muscle etc.). When the infusion is stopped, the drug redistributes from the peripheral tissues back into the blood, prolonging the effect.
Thiopental also exhibits zero order kinetics at higher doses. The rate of elimination becomes constant.
Patients with brain swelling, causing elevation of the intracranial pressure, either secondary to trauma or following surgery, may benefit from this drug. Thiopental, and the barbiturate class of drugs, decrease neuronal activity and therefore decrease the production of osmotically active metabolites, which in turn decreases swelling. Patients with significant swelling have improved outcomes following the induction of coma. Reportedly, thiopental has been shown to be superior to
pentobarbitalPentobarbital is a short-acting barbiturate that was first synthesized in 1928. Pentobarbital is available as both a free acid and a sodium salt, the former of which is only slightly soluble in water and ethanol....
in reducing intracranial pressure.This phenomena is also termed as Reverse steal Effect.
Euthanasia
Thiopental is used intravenously for the purposes of
euthanasiaEuthanasia refers to the practice of intentionally ending a life in order to relieve pain and suffering....
. The
BelgianBelgium , officially the Kingdom of Belgium, is a federal state in Western Europe. It is a founding member of the European Union and hosts the EU's headquarters, and those of several other major international organisations such as NATO.Belgium is also a member of, or affiliated to, many...
s and the
DutchThe Netherlands is a constituent country of the Kingdom of the Netherlands, located mainly in North-West Europe and with several islands in the Caribbean. Mainland Netherlands borders the North Sea to the north and west, Belgium to the south, and Germany to the east, and shares maritime borders...
have created a protocol that recommends sodium thiopental as the ideal agent to induce coma, followed by pancuronium bromide.
Intravenous administration is the most reliable and rapid way to accomplish euthanasia. A coma is first induced by intravenous administration of 20 mg/kg thiopental sodium (Nesdonal) in a small volume (10 ml physiological saline). Then, a triple dose of a non-depolarizing skeletal muscle relaxant is given, such as 20 mg pancuronium bromide (Pavulon) or 20 mg vecuronium bromide (Norcuron). The muscle relaxant should be given intravenously to ensure optimal availability but pancuronium bromide may be administered intramuscularly at an increased dosage level of 40 mg.
Lethal injection
Along with pancuronium bromide and
potassium chlorideThe chemical compound potassium chloride is a metal halide salt composed of potassium and chlorine. In its pure state, it is odorless and has a white or colorless vitreous crystal appearance, with a crystal structure that cleaves easily in three directions. Potassium chloride crystals are...
, thiopental is used in 34 states of the
U.S.The United States of America is a federal constitutional republic comprising fifty states and a federal district...
to execute prisoners by
lethal injectionLethal injection is the practice of injecting a person with a fatal dose of drugs for the express purpose of causing the immediate death of the subject. The main application for this procedure is capital punishment, but the term may also be applied in a broad sense to euthanasia and suicide...
. A very large dose is given to ensure rapid loss of consciousness. Although death usually occurs within ten minutes of the beginning of the injection process, some have been known to take longer. The use of sodium thiopental in execution protocols was challenged in court after a study in the medical journal
The LancetThe Lancet is a weekly peer-reviewed general medical journal. It is one of the world's best known, oldest, and most respected general medical journals...
reported autopsies of executed inmates showed the level of thiopental in their bloodstream was insufficient to cause unconsciousness.
On December 8, 2009, the State of Ohio became the first to use a single dose of sodium thiopental for its capital execution, following the failed use of the standard three-drug cocktail during a recent execution, due to inability to locate suitable veins.
Kenneth BirosKenneth Biros was an American convicted murderer who was sentenced to death and executed for the aggravated murder, attempted rape, aggravated robbery and felonious sexual penetration of a young woman...
was executed using the single-drug method. Death was pronounced at 11:47 a.m., about ten minutes after the single-dose injection was administered. Including the time required to insert the IV lines and prepare the inmate, the entire process lasted 43 minutes. Ohio executed a second man using sodium thiopental on January 7, 2010. Vernon Smith was pronounced dead eight minutes after the time of injection. A third man was executed using the single-drug method on April 20, 2010. Daryl Durr was pronounced dead at 10:36 am. Most recently, William Garner was executed in Ohio with sodium thiopental.
The state of Washington is now the second state in the U.S. to use the single-dose sodium thiopental injections for death penalty executions. On September 10, 2010, Cal Coburn Brown was executed. His was the first execution in the state to use a single dose, single drug injection. His death was pronounced approximately one and a half minutes after the intravenous administration of five grams of the drug.
Following a shortage that led a court to delay an execution in California, a company spokesman for
HospiraHospira, Inc. is a U.S.-based global pharmaceutical and medical device company with headquarters in Lake Forest, Illinois. It has approximately 14,000 employees. Hospira is the world's largest producer of generic injectable pharmaceuticals, manufacturing generic acute-care and oncology...
, the sole American manufacturer of the drug, expressed strong reservations about the use of thiopental in the lethal injection procedure. "Hospira manufactures this product because it improves or saves lives, and the company markets it solely for use as indicated on the product labeling. The drug is not indicated for capital punishment, and Hospira does not support its use in this procedure." On January 21, 2011, the company announced that it would stop production of sodium thiopental from its plant in Italy because it could not guarantee Italian authorities that the drug would not be used in executions. Italy was the only viable place where the company could produce sodium thiopental, leaving the United States without a supplier.
States such as Nebraska and South Dakota have turned to an Indian supplier of the drug but this move has been criticized on the grounds the chemical may deteriorate in transit to the United States.
A request from
Gary LockeGary Locke may refer to:*Gary Locke , Chinese American politician; U.S. Secretary of Commerce and former Governor of Washington*Gary Locke *Gary Locke...
to export thiopental for lethal injections was denied by the German government.
Truth serum
Thiopental (Pentothal) is still used in some places as a
truth serumA truth drug or truth serum is a psychoactive medication used to obtain information from subjects who are unable or unwilling to provide it otherwise. The unethical use of truth drugs is classified as a form of torture according to international law. However, they are properly and productively...
to weaken the resolve of the subject and make them more compliant to pressure. The barbiturates as a class decrease higher cortical brain functioning. Some psychiatrists hypothesize that because lying is more complex than telling the truth, suppression of the higher cortical functions may lead to the uncovering of the truth. The drug tends to make subjects chatty and cooperative with interrogators; however, the reliability of confessions made under thiopental is questionable.
Psychiatry
Psychiatrists have used thiopental to desensitize patients with
phobiaA phobia is a type of anxiety disorder, usually defined as a persistent fear of an object or situation in which the sufferer commits to great lengths in avoiding, typically disproportional to the actual danger posed, often being recognized as irrational...
s, and to "facilitate the recall of painful repressed memories." One psychiatrist who worked with thiopental is the
DutchThe Dutch people are an ethnic group native to the Netherlands. They share a common culture and speak the Dutch language. Dutch people and their descendants are found in migrant communities worldwide, notably in Suriname, Chile, Brazil, Canada, Australia, South Africa, New Zealand, and the United...
Professor Jan Bastiaans, who used this procedure to help relieve trauma in surviving victims of the Holocaust.
Metabolism
Thiopental rapidly and easily crosses the blood brain barrier as it is a lipophillic molecule. As with all lipid-soluble anaesthetic drugs, the short duration of action of sodium thiopental is due almost entirely to its redistribution away from central circulation towards muscle and fat tissue, due to its very high fat:water partition coefficient (aprx 10), leading to sequestration in fat tissue. Once redistributed, the free fraction in the blood is metabolised in the liver. Sodium thiopental is mainly metabolized to
pentobarbitalPentobarbital is a short-acting barbiturate that was first synthesized in 1928. Pentobarbital is available as both a free acid and a sodium salt, the former of which is only slightly soluble in water and ethanol....
, 5-ethyl-5-(1'-methyl-3'-hydroxybutyl)-2-thiobarbituric acid, and 5-ethyl-5-(1'-methyl-3'-carboxypropyl)-2-thiobarbituric acid.
Dosage
The usual dose range for induction of anesthesia using thiopental is from 3 to 7 mg/kg; however, there are many factors that can alter this. Premedication with sedatives such as benzodiazepines or
clonidineClonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...
will reduce requirements, as do specific disease states and other patient factors. Among patient factors are: age, sex, lean body mass. Specific disease conditions that can alter the dose requirements of thiopentone and for that matter any other intravenous anaesthetic are:
hypovolemiaIn physiology and medicine, hypovolemia is a state of decreased blood volume; more specifically, decrease in volume of blood plasma...
, burns,
azotemiaAzotemia is a medical condition characterized by abnormally high levels of nitrogen-containing compounds, such as urea, creatinine, various body waste compounds, and other nitrogen-rich compounds in the blood...
, hepatic failure,
hypoproteinemiaHypoproteinemia is a condition where there is an abnormally low level of protein in the blood.One common cause is due to excess protein in the urine , which can be a medical sign of nephrotic syndrome....
, etc.
Side effects
As with nearly all
anestheticAnesthesia, or anaesthesia , traditionally meant the condition of having sensation blocked or temporarily taken away...
drugA pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
s, thiopental causes cardiovascular and respiratory depression resulting in
hypotensionIn physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
,
apneaApnea, apnoea, or apnœa is a term for suspension of external breathing. During apnea there is no movement of the muscles of respiration and the volume of the lungs initially remains unchanged...
and
airwayThe pulmonary airway comprises those parts of the respiratory system through which air flows, conceptually beginning at the nose and mouth, and terminating in the alveoli...
obstruction. For these reasons, only suitably trained medical personnel should give thiopental in an environment suitably equipped to deal with these effects. Side effects include headache,
emergence deliriumDelirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...
, prolonged
somnolenceSomnolence is a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods . It has two distinct meanings, referring both to the usual state preceding falling asleep, and the chronic condition referring to being in that state independent of a circadian rhythm...
, and
nauseaNausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
. Intravenous administration of sodium thiopental is followed instantly by an odor and/or taste sensation, sometimes described as being similar to rotting onions, or to garlic. The hangover from the side effects may last up to 36 hours.
Although individual molecules of thiopental contain one
sulfurSulfur or sulphur is the chemical element with atomic number 16. In the periodic table it is represented by the symbol S. It is an abundant, multivalent non-metal. Under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a bright yellow...
atom, it is not a
sulfonamideIn chemistry, the sulfonamide functional group is -S2-NH2, a sulfonyl group connected to an amine group.A sulfonamide is a compound that contains this group. The general formula is RSO2NH2, where R is some organic group. For example, "methanesulfonamide" is CH3SO2NH2...
, and does not show allergic reactions of sulfa/sulpha drugs.
Contraindications
Thiopental should not be given in case of
liver diseaseLiver disease is a broad term describing any single number of diseases affecting the liver.-Diseases:* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons , autoimmunity or hereditary conditions...
,
Addison's diseaseAddison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...
,
myxedemaMyxedema describes a specific form of cutaneous and dermal edema secondary to increased deposition of connective tissue components in subcutaneous tissue as seen in various forms of hypothyroidism and Graves' disease. It is more common in women than in men...
, severe
heart diseaseHeart disease, cardiac disease or cardiopathy is an umbrella term for a variety of diseases affecting the heart. , it is the leading cause of death in the United States, England, Canada and Wales, accounting for 25.4% of the total deaths in the United States.-Types:-Coronary heart disease:Coronary...
, severe
hypotensionIn physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
, a severe breathing disorder, or a history of
porphyriaPorphyrias are a group of inherited or acquired disorders of certain enzymes in the heme bio-synthetic pathway . They are broadly classified as acute porphyrias and cutaneous porphyrias, based on the site of the overproduction and accumulation of the porphyrins...
.
Co-administration of
pentoxifylline and thiopental causes death by acute pulmonary oedema in rats. This pulmonary oedema was not mediated by cardiac failure or by
pulmonary hypertensionIn medicine, pulmonary hypertension is an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion...
but was due to increased pulmonary vascular permeability.
History
Sodium thiopental was discovered in the early 1930s by
Ernest H. VolwilerErnest Henry Volwiler spent his entire career at Abbott Laboratories working his way from staff chemist to CEO....
and Donalee L. Tabern, working for
Abbott LaboratoriesAbbott Laboratories is an American-based global, diversified pharmaceuticals and health care products company. It has 90,000 employees and operates in over 130 countries. The company headquarters are in Abbott Park, North Chicago, Illinois. The company was founded by Chicago physician, Dr....
. It was first used in human beings on March 8, 1934, by Dr. Ralph M. Waters in an investigation of its properties, which were short-term anesthesia and surprisingly little analgesia. Three months later, Dr. John S. Lundy started a clinical trial of thiopental at the
Mayo ClinicMayo Clinic is a not-for-profit medical practice and medical research group specializing in treating difficult patients . Patients are referred to Mayo Clinic from across the U.S. and the world, and it is known for innovative and effective treatments. Mayo Clinic is known for being at the top of...
at the request of Abbott. Abbott continued to make the drug until 2004, when it spun off its hospital-products division as Hospira.
Thiopental is famously associated with a number of anesthetic deaths in victims of the attack on
Pearl HarborPearl Harbor, known to Hawaiians as Puuloa, is a lagoon harbor on the island of Oahu, Hawaii, west of Honolulu. Much of the harbor and surrounding lands is a United States Navy deep-water naval base. It is also the headquarters of the U.S. Pacific Fleet...
. These deaths, relatively soon after the substance's discovery, were due to excessive doses given to shocked trauma patients. Evidence has become available through freedom of information legislation and has been reviewed in the "British Journal of Anaesthesia". Thiopental anaesthesia was in its early days, but nevertheless 13 of 344 wounded admitted to the
Tripler Army HospitalTripler Army Medical Center is the headquarters of the Pacific Regional Medical Command of the armed forces administered by the United States Army in the State of Hawaii. It is the largest military hospital in the Asian and Pacific Rim region and serves a military sphere of jurisdiction that spans...
did not survive.
Thiopental is still rarely used as a recreational drug, usually stolen from veterinarians or other legitimate users of the drug; however, more common sedatives such as benzodiazepines are usually preferred as recreational drugs, and abuse of thiopental tends to be uncommon and opportunistic.
Chemistry
Thiopental, 5-ethyl-5-(1-methylbutyl)2-thiobarbituric acid, is synthesized by the alkylation of ethylmalonic ester with 2-bromopentane in the presence of
sodium ethoxideSodium ethoxide is an alkoxide salt with the chemical formula C2H5ONa.-Preparation:It is commercially available as a white solid, or as a solution in ethanol. It is easily prepared in the laboratory by reacting sodium metal with ethanol:...
. The product ethyl-(1-methylbutyl)malonic ester undergoes heterocyclization with
thioureaThiourea is an organosulfur compound of with the formula SC2 . It is structurally similar to urea, except that the oxygen atom is replaced by a sulfur atom, but the properties of urea and thiourea differ significantly. Thiourea is a reagent in organic synthesis. "Thioureas" refers to a broad...
, using sodium ethoxide as a base.
- E.H. Volwlier, D.L. Tabern, (1939).
- G.H. Donaldson, W. Bay, (1959).
External links