Strychnine
Overview
 
Strychnine is a highly toxic ( = c. 16 mg/kg in rats, 1–2 mg/kg orally in humans ), colorless crystalline 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...

 used as a pesticide
Pesticide
Pesticides are substances or mixture of substances intended for preventing, destroying, repelling or mitigating any pest.A pesticide may be a chemical unicycle, biological agent , antimicrobial, disinfectant or device used against any pest...

, particularly for killing small vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...

s such as bird
Bird
Birds are feathered, winged, bipedal, endothermic , egg-laying, vertebrate animals. Around 10,000 living species and 188 families makes them the most speciose class of tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Extant birds range in size from...

s and rodent
Rodent
Rodentia is an order of mammals also known as rodents, characterised by two continuously growing incisors in the upper and lower jaws which must be kept short by gnawing....

s. Strychnine causes muscular convulsion
Convulsion
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 and eventually death through asphyxia
Asphyxia
Asphyxia or asphyxiation is a condition of severely deficient supply of oxygen to the body that arises from being unable to breathe normally. An example of asphyxia is choking. Asphyxia causes generalized hypoxia, which primarily affects the tissues and organs...

 or sheer exhaustion. The most common source is from the seeds of the Strychnos nux vomica
Strychnine tree
The Strychnine tree also known as Nux vomica, Poison Nut, Semen strychnos and Quaker Buttons, is a deciduous tree native to India, southeast Asia, a member of family Loganiaceae. It is a medium-size tree growing in open habitats...

tree.
Strychnine was the first alkaloid to be identified in plants of the genus Strychnos
Strychnos
Strychnos is a genus of flowering plants, belonging to family Loganiaceae . The genus includes about 190 species of trees and lianas, distributed around the world's tropics....

, Family Loganiaceae
Loganiaceae
Loganiaceae are a family of flowering plants classified in order Gentianales. The family includes 13 genera, distributed around the world's tropics.Earlier treatments of the family have included up to 29 genera...

.
Encyclopedia
Strychnine is a highly toxic ( = c. 16 mg/kg in rats, 1–2 mg/kg orally in humans ), colorless crystalline 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...

 used as a pesticide
Pesticide
Pesticides are substances or mixture of substances intended for preventing, destroying, repelling or mitigating any pest.A pesticide may be a chemical unicycle, biological agent , antimicrobial, disinfectant or device used against any pest...

, particularly for killing small vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...

s such as bird
Bird
Birds are feathered, winged, bipedal, endothermic , egg-laying, vertebrate animals. Around 10,000 living species and 188 families makes them the most speciose class of tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Extant birds range in size from...

s and rodent
Rodent
Rodentia is an order of mammals also known as rodents, characterised by two continuously growing incisors in the upper and lower jaws which must be kept short by gnawing....

s. Strychnine causes muscular convulsion
Convulsion
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 and eventually death through asphyxia
Asphyxia
Asphyxia or asphyxiation is a condition of severely deficient supply of oxygen to the body that arises from being unable to breathe normally. An example of asphyxia is choking. Asphyxia causes generalized hypoxia, which primarily affects the tissues and organs...

 or sheer exhaustion. The most common source is from the seeds of the Strychnos nux vomica
Strychnine tree
The Strychnine tree also known as Nux vomica, Poison Nut, Semen strychnos and Quaker Buttons, is a deciduous tree native to India, southeast Asia, a member of family Loganiaceae. It is a medium-size tree growing in open habitats...

tree.

History

Strychnine was the first alkaloid to be identified in plants of the genus Strychnos
Strychnos
Strychnos is a genus of flowering plants, belonging to family Loganiaceae . The genus includes about 190 species of trees and lianas, distributed around the world's tropics....

, Family Loganiaceae
Loganiaceae
Loganiaceae are a family of flowering plants classified in order Gentianales. The family includes 13 genera, distributed around the world's tropics.Earlier treatments of the family have included up to 29 genera...

. Strychnos, named by Carl Linnaeus in 1753, is a genus of trees and climbing shrubs of the gentian order. The genus contains 196 various species and is distributed throughout the warm regions of Asia (58 species), America (64 species), and Africa (75 species). The seeds and bark of many plants in this genus contain the powerful poison strychnine.

The toxic and medicinal effects of strychnine have been well known from the times of ancient China and India. The inhabitants of these countries had ancestral knowledge of the species nux vomica
Nux Vomica
Nux Vomica is the second album by The Veils, released on September 18 2006. It was recorded in Laurel Canyon and produced by Nick Launay, during spring of 2006. A far heavier and darker sound characterises Nux Vomica, very different from the indie sound of the previous record...

 and Saint-Ignatius’ bean. The species Strychnos nux-vomica is a tree native to Indonesia which attains a height of 12 m. The tree has a crooked, short, thick trunk and the wood is close grained and very durable. The fruit has an orange color and is about the size of a large apple with a hard rind and contains five seeds, which are covered with a soft wool-like substance. The ripe seeds look like flattened disks, which are very hard. These seeds are the chief commercial source of strychnine and were first imported to and marketed in Europe as a poison to kill rodents and small predators. Strychnos ignatii is a woody climbing shrub of the Philippines. The fruit of the plant, known as Saint Ignatius' bean, contains as many as 25 seeds embedded in the pulp. The seeds contain more strychnine than other commercial alkaloids. The properties of nux-vomica and Saint-Ignatius seeds are substantially those of the alkaloid strychnine.

Strychnine was first discovered by French chemists Joseph Bienaimé Caventou
Joseph Bienaimé Caventou
Joseph Bienaimé Caventou was a French chemist.He was a professor at the École de Pharmacie in Paris. He collaborated with Pierre-Joseph Pelletier in a Parisian laboratory located behind an apothecary. He was a pioneer in the use of mild solvents to isolate a number of active ingredients from...

 and Pierre-Joseph Pelletier in 1818 in the Saint-Ignatius’ bean. In some Strychnos plants a 9,10-dimethoxy derivative of strychnine, the alkaloid brucine
Brucine
Brucine is a bitter alkaloid closely related to strychnine. It occurs in several plant species, the most well known being the Strychnos nux-vomica tree, found in South-East Asia.While brucine is related to strychnine, it is not as poisonous...

, is also present. Brucine
Brucine
Brucine is a bitter alkaloid closely related to strychnine. It occurs in several plant species, the most well known being the Strychnos nux-vomica tree, found in South-East Asia.While brucine is related to strychnine, it is not as poisonous...

 is not as poisonous as strychnine. Historic records indicate that the strychnine alkaloid had been used to kill dogs, cats, and birds in Europe as far back as 1640. The structure of strychnine was first determined in 1946 by Sir Robert Robinson and in 1954 this alkaloid was synthesized in a laboratory by Robert B. Woodward
Robert Burns Woodward
Robert Burns Woodward was an American organic chemist, considered by many to be the preeminent organic chemist of the twentieth century...

. This is one of the most famous syntheses in the history of organic chemistry. Both chemists won the Nobel prize
Nobel Prize
The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...

 (Robinson in 1947 and Woodward in 1965).

Biosynthesis

Strychnine is a terpene
Terpene
Terpenes are a large and diverse class of organic compounds, produced by a variety of plants, particularly conifers, though also by some insects such as termites or swallowtail butterflies, which emit terpenes from their osmeterium. They are often strong smelling and thus may have had a protective...

 indole
Indole
Indole is an aromatic heterocyclic organic compound. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring. Indole is a popular component of fragrances and the precursor to many pharmaceuticals. Compounds that contain an...

 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...

 belonging to the Strychnos
Strychnos
Strychnos is a genus of flowering plants, belonging to family Loganiaceae . The genus includes about 190 species of trees and lianas, distributed around the world's tropics....

family of Corynanthe alkaloids, and it is derived from tryptamine
Tryptamine
Tryptamine is a monoamine alkaloid found in plants, fungi, and animals. It is based around the indole ring structure, and is chemically related to the amino acid tryptophan, from which its name is derived...

 and secologanin
Secologanin
Secologanin is a monoterpene synthesized from geranyl pyrophosphate in the mevalonate pathway. Secologanin then proceedes with dopamine to form ipecac alkaloids.-Biosynthesis:...

. The enzyme, strictosidine synthase
Strictosidine synthase
Strictosidine synthase a key enzyme in alkaloid biosynthesis. It catalyses the condensation of tryptamine with secologanin to form strictosidine:...

, catalyzes the condensation of tryptamine and secologanin, followed by a Pictet-Spengler reaction
Pictet-Spengler reaction
The Pictet–Spengler reaction is a chemical reaction in which a β-arylethylamine such as tryptamine undergoes ringclosure after condensation with an aldehyde or ketone. Usually an acidic catalyst is employed and the reaction mixture heated, but some reactive compounds give good yields even at...

 to form strictosidine. While the enzymes that catalyze the following steps have not been identified, the steps have been inferred by isolation of intermediates from Strychnos nux vomica. The next step is hydrolysis of the acetal
Acetal
An acetal is a molecule with two single-bonded oxygen atoms attached to the same carbon atom.Traditional usages distinguish ketals from acetals...

, which opens the ring by elimination of glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

 (O-Glu) and provides a reactive aldehyde. The nascent aldehyde is then attacked by a secondary amine to afford geissoschizine, a common intermediate of many related compounds in the Strychnos family.

A reverse Pictet-Spengler reaction cleaves the C2-C3 bond, while a subsequent Mannich reaction
Mannich reaction
The Mannich reaction is an organic reaction which consists of an amino alkylation of an acidic proton placed next to a carbonyl functional group with formaldehyde and ammonia or any primary or secondary amine. The final product is a β-amino-carbonyl compound also known as a Mannich base...

 forms the C3-C7 bond, and a Michael addition forms the C2-C16 bond to provide dehydropreakuammicine. Hydrolysis of the methyl ester and decarboxylation leads to norfluorocurarine. Stereospecific reduction of the endocyclic double bond by NADPH and hydroxylation
Hydroxylation
Hydroxylation is a chemical process that introduces a hydroxyl group into an organic compound. In biochemistry, hydroxylation reactions are often facilitated by enzymes called hydroxylases. Hydroxylation is the first step in the oxidative degradation of organic compounds in air...

 provides the Wieland-Gumlich aldehyde
Wieland-Gumlich aldehyde
The Wieland-Gumlich aldehyde is an indoline derived from strychnine. This compound is of some commercial interest as a chemical intermediate. It was first synthesized in 1932 by Wieland and Gumlich in 4 steps from strychnine...

, which was first isolated by Heimberger and Scott in 1973, although previously synthesized by Wieland and Gumlich in 1932. To elongate the appendage by 2 carbons, acetyl-CoA
Acetyl-CoA
Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester...

 is added to the aldehyde in an aldol reaction
Aldol reaction
The aldol reaction is a powerful means of forming carbon–carbon bonds in organic chemistry.Discovered independently by Charles-Adolphe Wurtz and Alexander Porfyrevich Borodin in 1872, the reaction combines two carbonyl compounds to form a new β-hydroxy carbonyl compound...

 to afford prestrychnine. Stychnine is then formed by a facile addition of the amine with the carboxylic acid or its activated CoA thioester
Thioester
Thioesters are compounds with the functional group C-S-CO-C. They are the product of esterification between a carboxylic acid and a thiol. Thioesters are widespread in biochemistry, the best-known derivative being acetyl-CoA.-Synthesis:...

, followed by ring-closure via displacement of an activated alcohol.

Toxicokinetics

There are multiple ways of exposure to strychnine. It mainly gets into the body via the oral route, inhalation or injection.
Oral:
Strychnine can be ingested as pills, pesticides and seeds of the plants (Strychnos of Loganiaceae species). It is quickly absorbed via the gastrointestinal tract, mainly via the intestine.
Inhalation:
When strychnine is sniffed or smoked, it is quickly absorbed by the mucous membranes.
Injection:
Strychnine is rapidly absorbed from the parenteral
Parenteral
Parenteral is a route of administration that involves piercing the skin or mucous membrane. Parenteral nutrition refers to providing nutrition via the veins.-Etymology:...

 (not via the gastrointestinal tract) sites of injection. If subcutaneously injected, the site of injection may affect the beginning of action.

Distribution

Strychnine is transported by plasma and erythrocytes. Due to slight protein binding, strychnine leaves the bloodstream quickly and distributes to the tissues. Approximately 50% of the ingested dose can enter the tissues in 5 minutes.
Also within a few minutes of ingestion, strychnine can be detected in the urine. Little difference was noted between oral and intramuscular administration of strychnine.
In persons killed by strychnine, the highest concentrations are found in the blood, liver, kidney and stomach wall. The usual fatal dose is 60–100 mg strychnine and is fatal after a period of 1–2 hours, though lethal doses vary depending on the individual.

Half-life

The half-life
Half-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...

 of strychnine is about 10 hours. This half-life
Half-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...

 suggests that normal hepatic function can efficiently degrade strychnine even when the quantity ingested is high enough to cause severe poisoning.

Metabolism

Strychnine is rapidly metabolized by the liver microsomal enzyme system requiring NADPH and O2.
Strychnine competes with the inhibitory neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

 glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...

 resulting in an excitatory state. However, the toxicokinetics
Toxicokinetics
Toxicokinetics is the description of what rate a chemical will enter the body and what happens to it once it is in the body. It is an application of pharmacokinetics to determine the relationship between the systemic exposure of a compound in experimental animals and its toxicity...

 after overdose have not been well described. In most severe cases of strychnine poisoning, the patient dies before reaching the hospital.

Elimination/ excretion

A few minutes after ingestion, strychnine is excreted unchanged in the urine, and accounts for about 5 to 15% of a sublethal dose given over 6 hours.
Approximately 10 to 20% of the dose will be excreted unchanged in the urine in the first 24 hours. The percentage excreted decreases with the increasing dose. Of the amount excreted by the kidneys, about 70% is excreted in the first 6 hours, and almost 90% in the first 24 hours. Excretion is almost complete in 48 to 72 hours.

Symptoms

Strychnine poisoning can be fatal to humans and animals and can occur by inhalation, swallowing or absorption through eyes or mouth, as explained above. It produces some of the most dramatic and painful symptoms of any known toxic reaction. For this reason, strychnine poisoning is often used in literature and film. It is also used as a rodenticide, but unfortunately it isn’t specific for unwanted pests.
Nux vomica seeds are effective only when they are crushed or chewed before swallowing. As the pericarp is quite hard and indigestible, if whole seeds are taken through mouth without chewing then usually there won’t be poisoning symptoms seen. The following are the main features:
  1. A severe nausea is seen, which may include vomiting due to the bitter taste.
  2. Since the whole nervous system is excited, convulsions affect all the muscles. As time goes on, the intervals between the convulsions become shorter, and the convulsions last longer.
  3. The face becomes cyanosed, with dilated pupils and prominent eye balls. The mouth may also froth. These symptoms are all due to spasms of the facial muscles.
  4. The body may be seen arch-shapes in following postures:
    1. Opisthotonus
      Opisthotonus
      Opisthotonus or opisthotonos, from Greek roots, opistho meaning "behind" and tonos meaning "tension", is a state of a severe hyperextension and spasticity in which an individual's head, neck and spinal column enter into a complete "bridging" or "arching" position...

      : Hyperextension. The person may be resting on heels and occipit.
    2. Emprosthotonos: The spasm of abdominal muscles may bend the body forward.
    3. Pleurothotonus
      Pleurothotonus
      Pleurothotonus, or commonly known as Pisa Syndrome, is a rare neurological syndrome which occurs due to prolonged exposure to antipsychotic drugs. It is characterized by dystonia, abnormal and sustained involuntary muscle contraction, which may cause twisting or jerking movements of the body or a...

      : The body may be flexed to one side.
  5. The person is conscious and the mind is clear until death.
  6. There is an immense reflex excitability. Even a small stimulus like light, noise or movement of the body may throw it into a spate of convulsions.
  7. Death usually occurs due to asphyxia as respiration is affected by muscle spasm.

Mechanism

Strychnine is a neurotoxin . It primarily affects the motor nerves in the spinal cord which control muscle contraction. An impulse is triggered at one end of a nerve by the binding of neurotransmitters to the receptors. In the presence of neuroinhibitors, a greater quantity of neurotransmitters must bind to receptors before there will be an action potential generated. An example of a neurotransmitter is glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...

, which acts primarily as an inhibitor when it binds to the glycine receptor
Glycine receptor
The glycine receptor, or GlyR, is the receptor for the amino acid neurotransmitter glycine. GlyR is an ionotropic receptor that produces its effects through chloride current...

. This is a ligand-gated chloride channel in neurons located in the spinal cord and in the brain. Strychnine is an antagonist
Antagonist
An antagonist is a character, group of characters, or institution, that represents the opposition against which the protagonist must contend...

 of glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...

, which means it binds to the same receptor. When strychnine binds to this receptor, glycine is unable to bind to it at the same time. Therefore, the inhibiting effect of glycine is reduced, so nerve impulses are triggered with lower levels of neurotransmitters. When there is no inhibitory effect the motor neurons do not stop their stimulus and the victim will have constant muscle contractions. Structure of strychnine in complex with ACh binding protein (AChBP). Brams et al, PLoS Biol 9:e1001034 2011

Strychnine is also an antagonist
Antagonist
An antagonist is a character, group of characters, or institution, that represents the opposition against which the protagonist must contend...

 for acetylcholine receptor
Acetylcholine receptor
An acetylcholine receptor is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.-Classification:...

s, which is known to be homologous to the glycine receptor.

In low dosages, strychnine can act as a stimulant and has been used by athletes to enhance their performance. Strychnine made headlines back in 1904 during the St. Louis Olympics
1904 Summer Olympics
The 1904 Summer Olympics, officially known as the Games of the III Olympiad, was an international multi-sport event which was celebrated in St. Louis, Missouri, in the United States from 1 July 1904, to November 23, 1904, at what is now known as Francis Field on the campus of Washington University...

. At that time there were no rules yet about the use of performance enhancing drugs. The American Fred Lorz won the marathon competition but was disqualified just after crossing the finish line because officials learned he had taken a car ride for part of the race. The next man to finish was the British athlete Thomas Hicks. He won the gold medal but not without a little help. About 10 miles from the finish line Hicks begged his trainers to let him stop running and give-up the race. His trainers refused and gave him a dose of strychnine as a stimulant to keep him going. They also gave him raw egg-white and brandy. As a result Hicks had to be carried across the finish line and it took four doctors to revive him so that he could leave the stadium.
More recently at the 1992 Barcelona Olympics, strychnine was used to optimize the athletic performance of a female volleyball player from China. This was Wu Dan and she was actually the first person to test positive for drugs at the Olympics. She tested positive for strychnine despite claiming not having ingested any. The strychnine was contained in capsules that Dan was taking without the knowledge of the team doctor. She took the capsule as a tonic because she was feeling a bit tired. The Olympic committee banned her from any more competition but stated that Dan didn’t intentionally cheat but the mistake was due to poor education.

Animal toxicity

Strychnine poisoning in animals occurs usually from ingestion of baits designed for use against gophers, moles and coyotes. Since 1990 in the United States most baits containing strychnine have been replaced with zinc-phosphide baits. In the Netherlands rodenticides with strychnine are forbidden.
Strychnine toxicity in rats is dependent on sex. It is more toxic to females than to males when administered via subcutaneous injection
Subcutaneous injection
A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, collectively referred to as the...

 or intraperitoneal injection
Intraperitoneal injection
Intraperitoneal injection or IP injection is the injection of a substance into the peritoneum . IP injection is more often applied to animals than humans...

. Differences are due to higher rates of metabolism by male rat liver microsomes. Dogs and cats are more susceptible among the domestic animals, pigs are believed to be as susceptible as dogs, and horses are able to tolerate relatively large amounts of strychnine. Birds affected by strychnine poisoning exhibit wing droop, salivation, tremors, muscle tenseness and convulsions. Death occurs as a result of respiratory arrest
Respiratory arrest
Respiratory arrest is the cessation of breathing. It is a medical emergency and it usually is related to or coincides with a cardiac arrest. Causes include opiate overdose, head injury, anaesthesia, tetanus, or drowning...

. The clinical signs of strychnine poisoning relate to its effects on the central nervous system
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...

. The first clinical signs of poisoning include nervousness, restlessness, twitching of the muscles, and stiffness of the neck. As the poisoning progresses, the muscular twitching becomes more pronounced and convulsions suddenly appear in all the skeletal muscles. The limbs are extended and the neck is curved to opisthotonus
Opisthotonus
Opisthotonus or opisthotonos, from Greek roots, opistho meaning "behind" and tonos meaning "tension", is a state of a severe hyperextension and spasticity in which an individual's head, neck and spinal column enter into a complete "bridging" or "arching" position...

. The pupils are widely dilated. As death approaches, the convulsions follow one another with increased rapidity, severity, and duration. Death results from asphyxia due to prolonged paralysis of the respiratory muscles. Following the ingestion of strychnine, symptoms of poisoning usually appear within 15 to 60 min. The LD50-values
LD50
In toxicology, the median lethal dose, LD50 , LC50 or LCt50 of a toxin, radiation, or pathogen is the dose required to kill half the members of a tested population after a specified test duration...

 for strychnine in animals are listed below in table 1.
The LD50 values for strychnine in animals
Organism Route LD50 (mg/kg)
Bird-wild Oral 16
Cat Intravenous 0.33
Cat Oral 0.5
Dog Intravenous 0.8
Dog Subcutaneous 0.35
Dog Oral 0.5
Duck Oral 3.0
Mouse Intraperitoneal 0.98
Mouse Intravenous 0.41
Mouse Oral 2.0
Mouse Parenteral 1.06
Mouse Subcutaneous 0.47
Pigeon Oral 21.0
Quail Oral 23.0
Rabbit Intravenous 0.4
Rabbit Oral 0.6
Rat Oral 16.0
rat Oral 2.35

Human toxicity

Strychnine is, as to most other animals, also very toxic to humans. The symptoms are generally the same as in other animals, because the mechanism is the same. The toxicity of strychnine in humans is not widely studied, for obvious reasons. The most information known today comes from real-life cases of strychnine poisoning, both unintentionally and intentionally. The LD50-values estimated from different cases of strychnine poisoning are listed below in table 2.
The LD50 values for strychnine in humans
Route LD50 (mg)
Human Oral 100-120
Human Oral 30-60
Human (child) Oral 15
Human (adult) Oral 50-100
Human (adult) Oral 30-100
Human (adult) Oral 30
Human Intravenously 5-10 (approximate)

Treatment

There is no specific 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"....

 for strychnine, but recovery from strychnine exposure is possible with early hospital treatment. Treatment consists of removing the drug from the body (decontamination
Decontamination
Decontamination is the process of cleansing the human body to remove contamination by hazardous materials including chemicals, radioactive substances, and infectious material...

) and getting supportive medical care in a hospital setting. Supportive care includes intravenous fluids, medications against convulsions and spasms, and cooling measures for high temperature. The patient should be kept in a quiet and darkened room, because excessive manipulation and loud noises may cause convulsions. Because these convulsions are extremely painful, an appropriate painkiller should be given. Treatment of strychnine poisoning involves an oral administration of activated charcoal which adsorbs
Adsorption
Adsorption is the adhesion of atoms, ions, biomolecules or molecules of gas, liquid, or dissolved solids to a surface. This process creates a film of the adsorbate on the surface of the adsorbent. It differs from absorption, in which a fluid permeates or is dissolved by a liquid or solid...

 any strychnine within the digestive tract. Unabsorbed strychnine can be removed from the stomach by gastric lavage
Gastric lavage
Gastric lavage, also commonly called stomach pumping or Gastric irrigation, is the process of cleaning out the contents of the stomach. It has been used for over 200 years as a means of eliminating poisons from the stomach. Such devices are normally used on a person who has ingested a poison or...

 with tannic acid
Tannic acid
Tannic acid is a specific commercial form of tannin, a type of polyphenol. Its weak acidity is due to the numerous phenol groups in the structure...

 (strong tea) or potassium permanganate solutions to oxidize strychnine. Gastric lavage is the process of cleaning out the contents of the stomach. Seizures are controlled by anticonvulsants, such as phenobarbital
Phenobarbital
Phenobarbital or phenobarbitone is a barbiturate, first marketed as Luminal by Friedr. Bayer et comp. It is the most widely used anticonvulsant worldwide, and the oldest still commonly used. It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the...

 or 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,...

, along with muscle relaxants such as dantrolene
Dantrolene
Dantrolene sodium is a muscle relaxant that acts by abolishing excitation-contraction coupling in muscle cells, probably by action on the ryanodine receptor. It is the only specific and effective treatment for malignant hyperthermia, a rare, life-threatening disorder triggered by general anesthesia...

 to combat muscle rigidity. 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 heavy doses of chloral
Chloral
Chloral, also known as trichloroacetaldehyde, is the organic compound with the formula Cl3CCHO. This aldehyde is a colourless oily liquid that is soluble in a wide range of solvents...

, bromide
Bromide
A bromide is a chemical compound containing bromide ion, that is bromine atom with effective charge of −1. The class name can include ionic compounds such as caesium bromide or covalent compounds such as sulfur dibromide.-Natural occurrence:...

, urethane
Urethane
Urethane can refer to*Carbamates, compounds with the functional group RONHR'*Ethyl carbamate, the colloquial name of which is urethane*Polyurethane in colloquial usage...

 or amyl nitrate
Amyl nitrate
Amyl nitrate is the chemical compound with the formula CH34ONO2. This molecule consists of the 5-carbon amyl group attached to a nitrate functional group. It is the ester of amyl alcohol and nitric acid.-Applications:...

 can also be used to restrain the convulsions. Because 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,...

, as the anticonvulsant of choice, is not effective in all cases, a combination with midazolam
Midazolam
Midazolam is a short-acting drug in the benzodiazepine class developed by Hoffmann-La Roche in the 1970s. The drug is used for treatment of acute seizures, moderate to severe insomnia, and for inducing sedation and amnesia before medical procedures. It possesses profoundly potent anxiolytic,...

, fentanyl, or pancuronium
Pancuronium
Pancuronium is a muscle relaxant with various purposes. It is the second of three drugs administered during most lethal injections in the United States.- Mode of action :...

 is recommended in controlling the convulsions. The fatal outcome of strychnine poisoning demands an aggressive management with early intubation, control of muscle tremors, and prevention of rhabdomyolysis
Rhabdomyolysis
Rhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure...

 and renal failure. If the patient survives the first 24 hours after poisoning then recovery is probable.

Murder and suicide cases

The most notable incidents which probably involved strychnine poisoning, are listed here.
  • Alexander the Great is believed to have been poisoned by strychnine in contaminated wine.
  • In the 19th century, strychnine was used by serial killer Thomas Neill Cream
    Thomas Neill Cream
    Dr. Thomas Neill Cream , also known as the Lambeth Poisoner, was a Scottish-born serial killer, who claimed his first proven victims in the United States and the rest in England, and possibly others in Canada and Scotland...

     in several murders on prostitutes in England.
  • Robert Johnson
    Robert Johnson
    Robert Leroy Johnson was an American blues singer and musician. His landmark recordings from 1936–37 display a combination of singing, guitar skills, and songwriting talent that have influenced later generations of musicians. Johnson's shadowy, poorly documented life and death at age 27 have given...

    , a famous blues artist, was supposedly killed after he drank a bottle of whiskey which was poisoned with strychnine.
  • Margot Begeman, a childhood friend of Vincent van Gogh
    Vincent van Gogh
    Vincent Willem van Gogh , and used Brabant dialect in his writing; it is therefore likely that he himself pronounced his name with a Brabant accent: , with a voiced V and palatalized G and gh. In France, where much of his work was produced, it is...

    , attempted suicide by ingesting strychnine.
  • Belle Gunnes, a woman from La Porte, Indiana, was a serial killer who allegedly used strychnine to kill some of her victims at the end of the 19th century.
  • Hannes Hirtzberger, the mayor of Spitz in Austria, was supposedly killed by local wine producer Helmut Osberger using strychnine.
  • Jane Stanford
    Jane Stanford
    Jane Stanford was the co-founder of Stanford University with her husband, Leland Stanford, whom she wed in 1850. She was the daughter of a shopkeeper and lived on Washington Avenue in Albany, New York, before her marriage...

    , co-founder of the Stanford University
    Stanford University
    The Leland Stanford Junior University, commonly referred to as Stanford University or Stanford, is a private research university on an campus located near Palo Alto, California. It is situated in the northwestern Santa Clara Valley on the San Francisco Peninsula, approximately northwest of San...

    , was probably killed by strychnine poisoning in the late 19th century.
  • Oskar Dirlewanger
    Oskar Dirlewanger
    Oskar Paul Dirlewanger was a World War II officer of the SS who commanded the SS-Sturmbrigade Dirlewanger, a penal battalion composed of German criminals...

    , the notorious leader of the SS Sturmbrigade Dirlewanger in the Second World War, was known to have murdered several Jews by having them injected with strychnine. He and his officers then watched them convulse until death, just for their entertainment.
  • A woman in San Diego, California, was poisoned with strychnine by her husband in 1990. Though he dialed 911, he did not mention his name or address, and rescue works had difficulty locating the victim. She eventually died in the hospital.

Fiction

Strychnine has also served as an inspiration in several books, movies and TV series.
  • In Agatha Christie
    Agatha Christie
    Dame Agatha Christie DBE was a British crime writer of novels, short stories, and plays. She also wrote romances under the name Mary Westmacott, but she is best remembered for her 66 detective novels and 14 short story collections , and her successful West End plays.According to...

    ’s novel “The Mysterious Affair at Styles
    The Mysterious Affair at Styles
    The Mysterious Affair at Styles is a detective novel by Agatha Christie. It was written in 1916 and was first published by John Lane in the United States in October 1920 and in the United Kingdom by The Bodley Head on January 21, 1921. The U.S...

    ”, Mrs. Emily Inglethorp was killed by strychnine poisoning.
  • Inmates in the TV series “The Wire
    The WIRE
    the WIRE is the student-run College radio station at the University of Oklahoma, broadcasting in a freeform format. The WIRE serves the University of Oklahoma and surrounding communities, and is staffed by student DJs. The WIRE broadcasts at 1710 kHz AM in Norman, Oklahoma...

    ” were given heroin doses laced with strychnine.
  • In Alfred Hitchcock
    Alfred Hitchcock
    Sir Alfred Joseph Hitchcock, KBE was a British film director and producer. He pioneered many techniques in the suspense and psychological thriller genres. After a successful career in British cinema in both silent films and early talkies, Hitchcock moved to Hollywood...

    ’s movie “Psycho”, Norman Bates’ mother and her lover were killed by strychnine poisoning.
  • In Peter Robinsons’ novel “Cold is the Grave”, Chief Constable Riddle’s daughter, Emily, is accidentally killed by cocaine laced with strychnine.
  • In J. Lee Thompsons’s movie “Cape Fear”, Max Cady poisons Sam Bowden’s dog with strychnine.
  • In the manga “Spiral: Suiri no Kizuna”, Ayumu Narumi takes strychnine after he is threatened by Rio Takeuchi to test his luck in a game.
  • In “All Creatures Great and Small”, the main character and veterinarian James Herriot has to deal with several dogs poisoned with strychnine when a dog-killer attacks the neighbourhood dogs.
  • In the episode “Mr Monk and the Secret Santa” of the TV series “Monk”, the murder is committed using a bottle of port poisoned with strychnine.
  • In the Elseworld graphical novel “Gotham by Gaslight”, the Joker makes a cameo. He tries to kill himself with strychnine but fails, and the muscle contractions leave him with a permanent grin.
    • In addition, a derivative of strychnine is sited as a key ingredient in the Joker's deadly toxic gas in the main continuity.
  • In William S. Burroughs
    William S. Burroughs
    William Seward Burroughs II was an American novelist, poet, essayist and spoken word performer. A primary figure of the Beat Generation and a major postmodernist author, he is considered to be "one of the most politically trenchant, culturally influential, and innovative artists of the 20th...

    's novel Naked Lunch
    Naked Lunch
    Naked Lunch is a novel by William S. Burroughs originally published in 1959. The book is structured as a series of loosely-connected vignettes. Burroughs stated that the chapters are intended to be read in any order...

    , strychnine is described as a "hot shot", a poisonous shot of heroin sold to informant
    Informant
    An informant is a person who provides privileged information about a person or organization to an agency. The term is usually used within the law enforcement world, where they are officially known as confidential or criminal informants , and can often refer pejoratively to the supply of information...

    s.
  • At the end of the movie Office Space
    Office Space
    Office Space is a 1999 American comedy film satirizing work life in a typical 1990s software company. Written and directed by Mike Judge, it focuses on a handful of individuals fed up with their jobs portrayed by Ron Livingston, Jennifer Aniston, Gary Cole, David Herman, Ajay Naidu, and Diedrich...

    , Milton mentions to a waiter "And yes, I won't be leaving a tip, 'cause I could... I could shut this whole resort down. Sir? I'll take my traveler's checks to a competing resort. I could write a letter to your board of tourism and I could have this place condemned. I could put... I could put... strychnine in the guacamole. There was salt on the glass, BIG grains of salt. "

See also

  • Avicide
    Avicide
    An avicide is any substance which can be used to kill birds.Commonly used avicides include strychnine, DRC-1339 and CPTH , and Avitrol . Chloralose is also used as an avicide...

  • Strychnine poisoning
    Strychnine poisoning
    Strychnine poisoning can be fatal to humans and other animals and can occur by inhalation, swallowing or absorption through eyes or mouth. It produces some of the most dramatic and painful symptoms of any known toxic reaction...

  • The Mysterious Affair at Styles
    The Mysterious Affair at Styles
    The Mysterious Affair at Styles is a detective novel by Agatha Christie. It was written in 1916 and was first published by John Lane in the United States in October 1920 and in the United Kingdom by The Bodley Head on January 21, 1921. The U.S...

  • "Poisoning Pigeons in the Park"
  • Wieland-Gumlich aldehyde
    Wieland-Gumlich aldehyde
    The Wieland-Gumlich aldehyde is an indoline derived from strychnine. This compound is of some commercial interest as a chemical intermediate. It was first synthesized in 1932 by Wieland and Gumlich in 4 steps from strychnine...

  • Denatonium
    Denatonium
    Denatonium, usually available as denatonium benzoate and as denatonium saccharide, is the bitterest chemical compound known; with bitterness thresholds of 0.05 ppm for the benzoate and 0.01 ppm for the saccharide.It was discovered in 1958 during research on local anesthetics by Macfarlan...

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