A convulsant is a drug which induces

convulsion A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a ...

s and/or

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

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 ...

. 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 ...

. Most convulsants are antagonists (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 ag ...

s) at either the GABA_A or glycine receptors, or ionotropic

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 syste ...

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,

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

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) 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 Sarin (NATO designation GB G-series, "B"">Nerve_agent#G-series.html" ;"title="hort for Nerve agent#G-series">G-series, "B" is an extremely toxic synthetic organophosphorus compound.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 ...

s, produce convulsions as a major part of their toxidrome, but also produce a number of other effects in the body and are usually classified separately. Dieldrin 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 Camphor () is a waxy, colorless solid with a strong aroma. It is classified as a terpenoid and a cyclic ketone. It is found in the wood of the camphor laurel ('' Cinnamomum camphora''), a large evergreen tree found in East Asia; and in the k ...

, 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 ar ...

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

s, etc.) in children who have had febrile seizures. __TOC__

Uses

Some convulsants such as pentetrazol and flurothyl were previously used in shock therapy 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 t ...

. Others such as

strychnine Strychnine (, , US chiefly ) is a highly toxic, colorless, bitter, crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine, when inhaled, swallowed, or absorbed through the ey ...

and tetramethylenedisulfotetramine are used as poisons for exterminating pests.

Bemegride Bemegride (trademarked as Megimide) is a central nervous system stimulant. The drug was first made in 1911. It has been used in hypnotic overdose. As with other chemoreceptor agonists, it is a potent emetic at doses above those normally used in m ...

and flumazenil 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 Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential as ...

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 ne ...

can lead to status epilepticus in animals as it is a cyclic analog of l-glutamate 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 dr ...

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. *

* Bicuculline * Cicutoxin * Cyclothiazide *

DMCM DMCM (methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate) is a drug from the β-carboline family. It acts as a negative allosteric modulator of GABAA receptors, meaning that it causes the opposite effects to the benzodiazepine class of drugs ...

* FG-7142 *

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 * Flurothyl *

Gabazine Gabazine (SR-95531) is a drug that acts as an antagonist at GABAA receptors. It is used in scientific research and has no role in medicine, as it would be expected to produce convulsions if used in humans. Gabazine binds to the GABA recognition ...

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. Gen ...

* Laudanosine * Oenanthotoxin * Pentylenetetrazol( Metrazol) * Phenylsilatrane *

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 * Sinomenine *

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 TBPS (''tert''-butylbicyclophosphorothionate) is a bicyclic ...

TBPS TBPS (''tert''-butylbicyclophosphorothionate) is a bicyclic phosphate convulsant. It is an extremely potent GABA receptor antagonist GABA receptor antagonists are drugs that inhibit the action of GABA. In general these drugs produce stimulant ...

* Tetramethylenedisulfotetramine *

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 respons ...

GABA synthesis inhibitors

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

Allylglycine Allylglycine is a glycine derivative. It is an inhibitor of glutamate decarboxylase. Inhibition of glutamate decarboxylase blocks GABA biosynthesis, leading to lower levels of the neurotransmitter. Allylglycine is known to induce seizures in an ...

Glycine receptor antagonists

Glycine receptor antagonist A glycine receptor antagonist is a drug which acts as an antagonist of the glycine receptor. Examples Antagonists * Selective ** Brucine ** Strychnine ** Tutin * Non-selective ** Bicuculline ** Caffeine ** Picrotoxin Picrotoxin, also known as ...

s are drugs which inactivates the glycine receptors. * Bicuculline * Brucine * Colubrine * Diaboline * Gelsemine * 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 comp ...

* RU-5135 (also GABA antagonist) * Sinomenine *

Strychnine Strychnine (, , US chiefly ) is a highly toxic, colorless, bitter, crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine, when inhaled, swallowed, or absorbed through the ey ...

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 simil ...

* Tutin

Ionotropic glutamate receptor agonists

Ionotropic glutamate receptor agonists are drugs that activate the ionotropic glutamate receptors 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 glutamaterg ...

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 ...

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 ne ...

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 *

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 ...

* Tetrazolylglycine

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 b ...

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 ab ...

Advantages

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 flurothyl 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