Aconitine
Encyclopedia
Aconitine is a highly poison
ous alkaloid
derived from various aconite
species.
that opens TTX
-sensitive Na+ channels
in the heart
and other tissues, and is used for creating models of cardiac arrhythmia. Aconitine was previously used as an antipyretic
and analgesic
, and still has some limited application in herbal medicine although the narrow therapeutic index
makes calculating appropriate dosage difficult.
in chloroform
or benzene
, slightly in alcohol
or ether
, and only very slightly in water
.
The Merck Index
gives s (i.e., median lethal dose 50%) for mice
: 0.166 mg/kg (intravenously); 0.328 mg/kg intraperitoneally (injected into the body cavity); approx. 1 mg/kg orally (ingested). In rats, the oral LD50 is given as 5.97 mg/kg. Oral doses as low as 1.5–6 mg aconitine were reported to be lethal in humans.
s, but also via skin. Respiratory paralysis, in very high doses also cardiac arrest
, leads to death. A few minutes after ingestion paresthesia
starts, which includes tingling in the oral region. This extends to the whole body, starting from the extremities. Anesthesia
, sweating and cooling of the body, nausea and vomiting and other similar symptoms follow. Sometimes there is strong pain, accompanied by cramps, or diarrhea. There is no antidote
, so only the symptoms can be treated, traditionally with compounds such as atropine
, strychnine
or barakol
, although it is unclear whether any of these are effective. Some other toxins such as tetrodotoxin
that bind to the same target site but have opposite effects can reduce the effects of aconitine, but are so toxic themselves that death may result nonetheless. The anti-dysrhythmic drug lidocaine, which is clinically used for treating unusual cardiac rhythms, also blocks these sodium channels and there is a single report of a successful treatment of accidental aconitine poisoning using this drug. Serum or urine concentrations of the chemical may be measured to confirm diagnosis in hospitalized poisoning victims, while postmortem blood levels have been reported in at least 5 fatal cases.
in 1881 to murder his brother-in-law in order to secure an inheritance. Lamson had learnt about aconitine as a medical student from Professor Robert Christison
, who had taught that it was undetectable—but forensic science had improved since Lamson's student days.
Aconitine was also made famous by its use in Oscar Wilde
's 1891 story Lord Arthur Savile's Crime. Aconite also plays a prominent role in James Joyce's Ulysses
, in which the protagonist Leopold Bloom's father used pastilles of the chemical to commit suicide.
In 1953 aconitine was used by a Soviet biochemist and poison developer Grigory Mairanovsky
in experiments with prisoners in the secret NKVD
laboratory in Moscow. He admitted killing around 10 people using the poison.
In 2009 Lakhvir Singh of Feltham
, west London, used aconitine to poison the food of her ex-lover (who died as a result of the poisoning) and his current fiancée. Singh received a life sentence for the murder.
It is used by Merlin in the TV series
(season 4 episode 6) to attempt to poison Arthur while under the negative influence of an enchantment.
Poison
In the context of biology, poisons are substances that can cause disturbances to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism....
ous alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
derived from various aconite
Aconitum
Aconitum , known as aconite, monkshood, wolfsbane, leopard's bane, women's bane, Devil's helmet or blue rocket, is a genus of over 250 species of flowering plants belonging to the buttercup family .-Overview:These herbaceous perennial plants are chiefly natives of the mountainous parts of the...
species.
Uses
It is a neurotoxinNeurotoxin
A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...
that opens TTX
Tetrodotoxin
Tetrodotoxin, also known as "tetrodox" and frequently abbreviated as TTX, sometimes colloquially referred to as "zombie powder" by those who practice Vodou, is a potent neurotoxin with no known antidote. There have been successful tests of a possible antidote in mice, but further tests must be...
-sensitive Na+ channels
Sodium ion channel
Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions through a cell's plasma membrane. They are classified according to the trigger that opens the channel for such ions, i.e...
in the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
and other tissues, and is used for creating models of cardiac arrhythmia. Aconitine was previously used as an antipyretic
Antipyretic
Antipyretics ; an-tee-pahy-ret-iks; from the Greek anti, against, and pyreticus, are drugs or herbs that reduce fever. Normally, they will not lower body temperature if one does not have a fever. Antipyretics cause the hypothalamus to override an interleukin-induced increase in temperature...
and analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
, and still has some limited application in herbal medicine although the narrow therapeutic index
Therapeutic index
The therapeutic index is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes death or toxicity ....
makes calculating appropriate dosage difficult.
Composition
Aconitine has the chemical formula C34H47NO11, and is solubleSolubility
Solubility is the property of a solid, liquid, or gaseous chemical substance called solute to dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the solute in the solvent. The solubility of a substance fundamentally depends on the used solvent as well as on...
in chloroform
Chloroform
Chloroform is an organic compound with formula CHCl3. It is one of the four chloromethanes. The colorless, sweet-smelling, dense liquid is a trihalomethane, and is considered somewhat hazardous...
or benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....
, slightly in alcohol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
or ether
Diethyl ether
Diethyl ether, also known as ethyl ether, simply ether, or ethoxyethane, is an organic compound in the ether class with the formula . It is a colorless, highly volatile flammable liquid with a characteristic odor...
, and only very slightly in water
Water
Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...
.
The Merck Index
Merck Index
The Merck Index is an encyclopedia of chemicals, drugs and biologicals with over 10,000 monographs on single substances or groups of related compounds. It also includes an appendix with monographs on organic name reactions. It is published by the United States pharmaceutical company Merck & Co...
gives s (i.e., median lethal dose 50%) for mice
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...
: 0.166 mg/kg (intravenously); 0.328 mg/kg intraperitoneally (injected into the body cavity); approx. 1 mg/kg orally (ingested). In rats, the oral LD50 is given as 5.97 mg/kg. Oral doses as low as 1.5–6 mg aconitine were reported to be lethal in humans.
Effects
It is quickly absorbed via mucous membraneMucous membrane
The mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...
s, but also via skin. Respiratory paralysis, in very high doses also cardiac arrest
Cardiac arrest
Cardiac arrest, is the cessation of normal circulation of the blood due to failure of the heart to contract effectively...
, leads to death. A few minutes after ingestion paresthesia
Paresthesia
Paresthesia , spelled "paraesthesia" in British English, is a sensation of tingling, burning, pricking, or numbness of a person's skin with no apparent long-term physical effect. It is more generally known as the feeling of "pins and needles" or of a limb "falling asleep"...
starts, which includes tingling in the oral region. This extends to the whole body, starting from the extremities. Anesthesia
Anesthesia
Anesthesia, or anaesthesia , traditionally meant the condition of having sensation blocked or temporarily taken away...
, sweating and cooling of the body, nausea and vomiting and other similar symptoms follow. Sometimes there is strong pain, accompanied by cramps, or diarrhea. There is no antidote
Antidote
An antidote is a substance which can counteract a form of poisoning. The term ultimately derives from the Greek αντιδιδοναι antididonai, "given against"....
, so only the symptoms can be treated, traditionally with compounds such as atropine
Atropine
Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...
, strychnine
Strychnine
Strychnine is a highly toxic , colorless crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine causes muscular convulsions and eventually death through asphyxia or sheer exhaustion...
or barakol
Barakol
Barakol is a compound found in the plant Senna siamea, which is used in traditional herbal medicine. It has sedative and anxiolytic effects, but use for these purposes is now discouraged due to hepatotoxicity....
, although it is unclear whether any of these are effective. Some other toxins such as tetrodotoxin
Tetrodotoxin
Tetrodotoxin, also known as "tetrodox" and frequently abbreviated as TTX, sometimes colloquially referred to as "zombie powder" by those who practice Vodou, is a potent neurotoxin with no known antidote. There have been successful tests of a possible antidote in mice, but further tests must be...
that bind to the same target site but have opposite effects can reduce the effects of aconitine, but are so toxic themselves that death may result nonetheless. The anti-dysrhythmic drug lidocaine, which is clinically used for treating unusual cardiac rhythms, also blocks these sodium channels and there is a single report of a successful treatment of accidental aconitine poisoning using this drug. Serum or urine concentrations of the chemical may be measured to confirm diagnosis in hospitalized poisoning victims, while postmortem blood levels have been reported in at least 5 fatal cases.
Aconitine poisoners
Aconitine was the poison used by George Henry LamsonGeorge Henry Lamson
George Henry Lamson was an American doctor and murderer.In his early career he had been a volunteer surgeon in Romania and Serbia, and decorated for his work. He returned to England and practised in Bournemouth...
in 1881 to murder his brother-in-law in order to secure an inheritance. Lamson had learnt about aconitine as a medical student from Professor Robert Christison
Robert Christison
Sir Robert Christison, 1st Baronet FRSE FRCSE FRCPE was a Scottish toxicologist and physician who served as president of the Royal College of Surgeons of Edinburgh , as president of the Royal College of Physicians of Edinburgh , and as president of the British Medical Association .Christison was...
, who had taught that it was undetectable—but forensic science had improved since Lamson's student days.
Aconitine was also made famous by its use in Oscar Wilde
Oscar Wilde
Oscar Fingal O'Flahertie Wills Wilde was an Irish writer and poet. After writing in different forms throughout the 1880s, he became one of London's most popular playwrights in the early 1890s...
's 1891 story Lord Arthur Savile's Crime. Aconite also plays a prominent role in James Joyce's Ulysses
Ulysses (novel)
Ulysses is a novel by the Irish author James Joyce. It was first serialised in parts in the American journal The Little Review from March 1918 to December 1920, and then published in its entirety by Sylvia Beach on 2 February 1922, in Paris. One of the most important works of Modernist literature,...
, in which the protagonist Leopold Bloom's father used pastilles of the chemical to commit suicide.
In 1953 aconitine was used by a Soviet biochemist and poison developer Grigory Mairanovsky
Grigory Mairanovsky
Grigory Mairanovsky was a Soviet biochemist and poison developer.He was head of secret laboratories in the Bach Institute of Biochemistry in Moscow . As the head of Laboratory No. 1 of the NKVD , he initiated the secret "scientific" poison program conducted by the Soviet secret police services...
in experiments with prisoners in the secret NKVD
NKVD
The People's Commissariat for Internal Affairs was the public and secret police organization of the Soviet Union that directly executed the rule of power of the Soviets, including political repression, during the era of Joseph Stalin....
laboratory in Moscow. He admitted killing around 10 people using the poison.
In 2009 Lakhvir Singh of Feltham
Feltham
Feltham is a town in the London Borough of Hounslow, west London. It is located about west south west of central London at Charing Cross and from Heathrow Airport Central...
, west London, used aconitine to poison the food of her ex-lover (who died as a result of the poisoning) and his current fiancée. Singh received a life sentence for the murder.
It is used by Merlin in the TV series
Merlin (TV series)
Merlin is a British fantasy-adventure television programme by Julian Jones, Jake Michie, Julian Murphy and Johnny Capps. It began broadcasting on BBC One on 20 September 2008. The show is based on the Arthurian legends of the wizard Merlin and his relationship with Prince Arthur but differs from...
(season 4 episode 6) to attempt to poison Arthur while under the negative influence of an enchantment.