A convulsant is a drug which induces convulsions and/or

epileptic seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...

s, the opposite of an

anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...

. These drugs generally act as

stimulant Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...

s at low doses, but are not used for this purpose due to the risk of convulsions and consequent

excitotoxicity In excitotoxicity, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high, resulting in excessive stimulation of receptors. For example, when glutamate re ...

. Most convulsants are

antagonists An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

(or

inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agon ...

s) at either the GABA_A or

glycine receptor The glycine receptor (abbreviated as GlyR or GLR) is the receptor of the amino acid neurotransmitter glycine. GlyR is an ionotropic receptor that produces its effects through chloride current. It is one of the most widely distributed inhibitory ...

s, or

ionotropic Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in res ...

glutamate receptor Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate (the conjugate base of glutamic acid) is abundant in the human body, but particularly in the nervous system ...

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

s. Many other drugs may cause convulsions as a side effect at high doses (e.g. bupropion,

tramadol Tramadol, sold under the brand name Ultram among others, is an opioid pain medication used to treat moderate to moderately severe pain. When taken by mouth in an immediate-release formulation, the onset of pain relief usually begins within an ...

pethidine Pethidine, also known as meperidine and sold under the brand name Demerol among others, is a synthetic opioid analgesic, pain medication of the phenylpiperidine class. Synthesized in 1938 as a potential anticholinergic agent by the German chemis ...

dextropropoxyphene Dextropropoxyphene is an analgesic in the opioid category, patented in 1955 and manufactured by Eli Lilly and Company. It is an optical isomer of levopropoxyphene. It is intended to treat mild pain and also has antitussive (cough suppressant) ...

clomipramine Clomipramine, sold under the brand name Anafranil among others, is a tricyclic antidepressant (TCA). It is used for the treatment of obsessive–compulsive disorder, panic disorder, major depressive disorder, and chronic pain. It may increase th ...

) but only drugs whose primary action is to cause convulsions are known as convulsants.

Nerve agent Nerve agents, sometimes also called nerve gases, are a class of organic chemicals that disrupt the mechanisms by which nerves transfer messages to organs. The disruption is caused by the blocking of acetylcholinesterase (AChE), an enzyme that ...

s such as sarin, which were developed as

chemical weapon A chemical weapon (CW) is a specialized munition that uses chemicals formulated to inflict death or harm on humans. According to the Organisation for the Prohibition of Chemical Weapons (OPCW), this can be any chemical compound intended as a ...

s, produce convulsions as a major part of their

toxidrome A toxidrome (a portmanteau of ''toxic'' and ''syndrome'') is a syndrome caused by a dangerous level of toxins in the body. The term was coined in 1970 by Mofenson and Greensher. It is often the consequence of a drug overdose. Common symptoms incl ...

, but also produce a number of other effects in the body and are usually classified separately.

Dieldrin Dieldrin is an organochloride originally produced in 1948 by J. Hyman & Co, Denver, as an insecticide. Dieldrin is closely related to aldrin, which reacts further to form dieldrin. Aldrin is not toxic to insects; it is oxidized in the insect to fo ...

which was developed as an insecticide blocks chloride influx into the neurons causing hyperexcitability of the CNS and convulsions. The Irwin observation test and other studies that record clinical signs are used to test the potential for a drug to induce convulsions. Camphor, and other

terpene Terpenes () are a class of natural products consisting of compounds with the formula (C5H8)n for n > 1. Comprising more than 30,000 compounds, these unsaturated hydrocarbons are produced predominantly by plants, particularly conifers. Terpenes ...

s given to children with colds can act as convulsants ( sympathomimetics,

piperazine Piperazine () is an organic compound that consists of a six-membered ring containing two nitrogen atoms at opposite positions in the ring. Piperazine exists as small alkaline deliquescent crystals with a saline taste. The piperazines are a broad ...

derivatives, theophilline,

antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provid ...

s, etc.) in children who have had

febrile seizure A febrile seizure, also known as a fever fit or febrile convulsion, is a seizure associated with an increased body temperature Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even whe ...

s. __TOC__

Uses

Some convulsants such as

pentetrazol Pentylenetetrazol, also known as pentylenetetrazole, leptazol, metrazol, pentetrazol (INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country ...

and

flurothyl Flurothyl (Indoklon) (IUPAC names: 1,1,1-trifluoro-2-(2,2,2-trifluoroethoxy)ethane or bis(2,2,2-trifluoroethyl) ether) is a volatile liquid drug from the halogenated ether family, related to inhaled anaesthetic agents such as diethyl ether, b ...

were previously used in

shock therapy Electroconvulsive therapy (ECT) is a psychiatric treatment where a generalized seizure (without muscular convulsions) is electrically induced to manage refractory mental disorders.Rudorfer, MV, Henry, ME, Sackeim, HA (2003)"Electroconvulsive the ...

in psychiatric medicine, as an alternative to

electroconvulsive therapy Electroconvulsive therapy (ECT) is a psychiatric treatment where a generalized seizure (without muscular convulsions) is electrically induced to manage refractory mental disorders.Rudorfer, MV, Henry, ME, Sackeim, HA (2003)"Electroconvulsive th ...

. Others such as strychnine and

tetramethylenedisulfotetramine Tetramethylenedisulfotetramine (TETS) is an organic compound used as a rodenticide (rat poison). It is an odorless, tasteless white powder that is slightly soluble in water, DMSO and acetone, and insoluble in methanol and ethanol. It is a sulfamid ...

are used as poisons for exterminating pests. Bemegride and

flumazenil Flumazenil (also known as flumazepil, code name Ro 15-1788) is a selective GABAA receptor antagonist administered via injection, otic insertion, or intranasally. Therapeutically, it acts as both an antagonist and antidote to benzodiazepines ( ...

are used to treat drug

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended.

s (of barbiturates and

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

s respectively), but may cause convulsions if the dose is too high. Convulsants are also widely used in scientific research, for instance in the testing of new anticonvulsant drugs. Convulsions are induced in captive animals, then high doses of anticonvulsant drugs are administered. For example,

kainic acid Kainic acid, or kainate, is an acid that naturally occurs in some seaweed. Kainic acid is a potent neuroexcitatory amino acid agonist that acts by activating receptors for glutamate, the principal excitatory neurotransmitter in the central nervo ...

can lead to status epilepticus in animals as it is a cyclic analog of

l-glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...

and an agonist for

kainate receptor Kainate receptors, or kainic acid receptors (KARs), are ionotropic receptors that respond to the neurotransmitter glutamate. They were first identified as a distinct receptor type through their selective activation by the agonist kainate, a dru ...

s in the brain which makes it a potent neurotoxin and excitant.

Examples

GABA_A receptor antagonists, inverse agonists or negative allosteric modulators

GABA_A receptor antagonists are drugs that bind to GABA_A receptors but do not activate them and inhibit the action of GABA. Thus it blocks both the endogenous and exogenous actions of GABA_A receptor agonists. * Bemegride * Bicuculline * Cicutoxin *

Cyclothiazide Cyclothiazide (Anhydron, Acquirel, Doburil, Fluidil, Renazide, Tensodiural, Valmiran), sometimes abbreviated CTZ, is a benzothiadiazide (thiazide) diuretic and antihypertensive that was originally introduced in the United States in 1963 by Eli L ...

* DMCM *

FG-7142 FG-7142 (ZK-31906) is a drug which acts as a partial inverse agonist at the benzodiazepine allosteric site of the GABAA receptor. It has anorectic, anxiogenic and pro-convulsant effects. It also increases release of acetylcholine and noradrenalin ...

Fipronil Fipronil is a broad-spectrum insecticide that belongs to the phenylpyrazole chemical family. Fipronil disrupts the insect central nervous system by blocking the ligand-gated ion channel of the GABAA receptor and glutamate-gated chloride (GluCl ...

Flumazenil Flumazenil (also known as flumazepil, code name Ro 15-1788) is a selective GABAA receptor antagonist administered via injection, otic insertion, or intranasally. Therapeutically, it acts as both an antagonist and antidote to benzodiazepines ( ...

Flurothyl Flurothyl (Indoklon) (IUPAC names: 1,1,1-trifluoro-2-(2,2,2-trifluoroethoxy)ethane or bis(2,2,2-trifluoroethyl) ether) is a volatile liquid drug from the halogenated ether family, related to inhaled anaesthetic agents such as diethyl ether, b ...

Gabazine Gabazine (SR-95531) is a drug that acts as an Receptor antagonist, antagonist at GABAA receptor, GABAA Receptor (biochemistry), receptors. It is used in scientific research and has no role in medicine, as it would be expected to produce convulsio ...

IPTBO IPTBO (isopropylbicyclophosphate, also IPPO) is a bicyclic phosphate convulsant. It is an extremely potent GABA receptor antagonist that can cause violent convulsions in mice. IPTBO is found among a group of highly toxic bicyclic phosphates. Ge ...

* Laudanosine * Oenanthotoxin *

Pentylenetetrazol Pentylenetetrazol, also known as pentylenetetrazole, leptazol, metrazol, pentetrazol (INN), pentamethylenetetrazol, Corazol, Cardiazol, Deumacard, or PTZ, is a drug formerly used as a circulatory and respiratory stimulant. High doses cause convul ...

(

Metrazol Pentylenetetrazol, also known as pentylenetetrazole, leptazol, metrazol, pentetrazol (INN), pentamethylenetetrazol, Corazol, Cardiazol, Deumacard, or PTZ, is a drug formerly used as a circulatory and respiratory stimulant. High doses cause convul ...

) *

Phenylsilatrane Phenylsilatrane is a convulsant chemical which has been used as a rodenticide. Phenylsilatrane and some of its analogs with 4-substituents of H, CH3, Cl, Br, and CSi(CH3)3 are highly toxic to mice. They have been observed in the laboratory to inh ...

Picrotoxin Picrotoxin, also known as cocculin, is a poisonous crystalline plant compound. It was first isolated by the French pharmacist and chemist Pierre François Guillaume Boullay (1777–1869) in 1812. The name "picrotoxin" is a combination of the Gree ...

Sarmazenil Sarmazenil (Ro15-3505) is a drug from the benzodiazepine family. It acts as a partial inverse agonist of benzodiazepine receptors, meaning that it causes the opposite effects to most benzodiazepine drugs, and instead acts as an anxiogenic and con ...

Securinine Securinine is an alkaloid found in ''Securinega suffruticosa'' and ''Phyllanthus niruri''. Pharmacology Securinine has pro-convulsant effects and it has a strong Spasticity, spastic effect, similar to the actions of strychnine. Securinine is ...

Sinomenine Sinomenine or cocculine is an alkaloid found in the root of the climbing plant '' Sinomenium acutum'' which is native to Japan and China. The plant is traditionally used in herbal medicine in these countries for rheumatism and arthritis. Howev ...

TBPO TBPO is an extremely toxic bicyclic phosphate convulsant and GABA receptor antagonist. It is the most toxic bicyclic phosphate known, with an of 36 μg/kg in mice. See also *TBPS *IPTBO IPTBO (isopropylbicyclophosphate, also IPPO) is a bicycl ...

TBPS TBPS (''tert''-butylbicyclophosphorothionate) is a bicyclic phosphate convulsant. It is an extremely potent GABA receptor antagonist. See also *IPTBO *EBOB EBOB is a GABA receptor antagonist and neurotoxin. See also * TBPS *IPTBO IPTBO (is ...

Tetramethylenedisulfotetramine Tetramethylenedisulfotetramine (TETS) is an organic compound used as a rodenticide (rat poison). It is an odorless, tasteless white powder that is slightly soluble in water, DMSO and acetone, and insoluble in methanol and ethanol. It is a sulfamid ...

Thujone Thujone () is a ketone and a monoterpene that occurs predominantly in two diastereomeric (epimeric) forms: (−)-α-thujone and (+)-β-thujone. Though it is best known as a chemical compound in the spirit absinthe, it is unlikely to be responsib ...

GABA synthesis inhibitors

GABA synthesis inhibitors are drugs that inhibit the action of GABA. * 3-Mercaptopropionic acid * Allylglycine

Glycine receptor antagonists

Glycine receptor antagonists are drugs which inactivates the glycine receptors. * Bicuculline *

Brucine Brucine, is an alkaloid closely related to strychnine, most commonly found in the ''Strychnos nux-vomica'' tree. Brucine poisoning is rare, since it is usually ingested with strychnine, and strychnine is more toxic than brucine. In synthetic ch ...

Colubrine The Colubrinae are a subfamily of the family Colubridae of snakes. It includes numerous genera, and although taxonomic sources often disagree on the exact number, The Reptile Database lists 717 species in 92 genera as of September 2019. It i ...

* Diaboline *

Gelsemine Gelsemine (C20H22N2O2) is an indole alkaloid isolated from flowering plants of the genus ''Gelsemium'', a plant native to the subtropical and tropical Americas, and southeast Asia, and is a highly toxic compound that acts as a paralytic, exposu ...

* Hyenandrine * Laudanosine *

Oripavine Oripavine is an opioid and the major metabolite of thebaine. It is the parent compound from which a series of semi-synthetic opioids are derived, which includes the compounds etorphine and buprenorphine. Although its analgesic potency is compar ...

* RU-5135 (also GABA antagonist) *

* Strychnine *

Thebaine Thebaine (paramorphine), also known as codeine methyl enol ether, is an opiate alkaloid, its name coming from the Greek Θῆβαι, '' Thēbai'' (Thebes), an ancient city in Upper Egypt. A minor constituent of opium, thebaine is chemically similar ...

Tutin Tutin may refer to: Places *Tutin, Serbia, town in Serbia Surname *Arthur Tutin (1907–1961), English footballer *Dorothy Tutin (1930–2001), English actress *Mary Tutin, maiden name of Mary Gillick (1881–1965), English sculptor *Tom Tutin (1 ...

Ionotropic glutamate receptor agonists

Ionotropic glutamate receptor agonists are drugs that activate the

ionotropic glutamate receptor Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that are activated by the neurotransmitter glutamate. They mediate the majority of excitatory synaptic transmission throughout the central nervous system and are key players in ...

s in the brain. *

AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, better known as AMPA, is a compound that is a specific agonist for the AMPA receptor, where it mimics the effects of the neurotransmitter glutamate. There are several types of glutamatergic ...

Domoic acid Domoic acid (DA) is a kainic acid-type neurotoxin that causes amnesic shellfish poisoning (ASP). It is produced by algae and accumulates in shellfish, sardines, and anchovies. When sea lions, otters, cetaceans, humans, and other predators eat c ...

Kainic acid Kainic acid, or kainate, is an acid that naturally occurs in some seaweed. Kainic acid is a potent neuroexcitatory amino acid agonist that acts by activating receptors for glutamate, the principal excitatory neurotransmitter in the central nervo ...

NMDA ''N''-methyl--aspartic acid or ''N''-methyl--aspartate (NMDA) is an amino acid derivative that acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor. Unlike ...

Quinolinic acid Quinolinic acid (abbreviated QUIN or QA), also known as pyridine-2,3-dicarboxylic acid, is a dicarboxylic acid with a pyridine backbone. It is a colorless solid. It is the biosynthetic precursor to niacin. Quinolinic acid is a downstream produ ...

Quisqualic acid Quisqualic acid is an agonist of the AMPA, kainate, and group I metabotropic glutamate receptors. It is one of the most potent AMPA receptor agonists known. It causes excitotoxicity and is used in neuroscience to selectively destroy neurons in ...

Tetrazolylglycine Tetrazolylglycine (Tet-Gly, LY-285,265) is a potent and selective NMDA receptor agonist, stimulating the NMDA receptor with higher potency than either glutamate or NMDA. It is a potent convulsant and excitotoxin In excitotoxicity, nerve cells ...

Acetylcholine receptor agonists

Acetylcholine receptor agonists are drugs that activate the acetylcholine receptors. *

Anatoxin-a Anatoxin-a, also known as Very Fast Death Factor (VFDF), is a secondary, bicyclic amine alkaloid and cyanotoxin with acute neurotoxicity. It was first discovered in the early 1960s in Canada, and was isolated in 1972. The toxin is produced by mu ...

Pilocarpine Pilocarpine is a medication used to reduce pressure inside the eye and treat dry mouth. As eye drops it is used to manage angle closure glaucoma until surgery can be performed, ocular hypertension, primary open angle glaucoma, and to bring abo ...

Advantages

Camphor injections for psychiatric treatment were inefficient and were replaced by phentylenetetrazol. Seizures induced by chemicals like flurothyl were clinically effective as electric convulsions with lesser side effects on memory retention. Therefore, considering flurothyl induced seizures in modern anesthesia facilities is encouraged to relieve medication treatment resistant patients with psychiatric illnesses like mood disorders and catatonia.

Risks/Complications

Convulsants like phentylenetetrazol and

were effective in psychiatric treatment but difficult to administer. Flurothyl was not widely being used due to the persistence of the ethereal aroma and fears in the professional staff that they might seize.

History

In 1934, camphor-induced and phentylenetetrazol-induced brain seizures were first used to relieve psychiatric illnesses. But camphor was found ineffective. In 1957, inhalant anesthetic flurothyl was tested and found to be clinically effective in the induction of seizures, even though certain risks persisted.

References

{{Convulsants