A convulsant is a drug which induces convulsions or epileptic seizures, the opposite of an anticonvulsant. These drugs generally act as

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

s at low doses, but are not used for this purpose due to poor therapeutic indices. Most convulsants are antagonists (or inverse agonists) at either the GABA_A or/and glycine receptors (e.g the pesticide fipronil), or ionotropic glutamate receptor

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

s (e.g the marine toxin

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 cont ...

). Many other drugs may cause convulsions as a side effect at high doses (e.g. bupropion, tramadol, pethidine, dextropropoxyphene, 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 chemistry, organic chemicals that disrupt the mechanisms by which nerves transfer messages to organs. The disruption is caused by the blocking of acetylcholinesterase (ACh ...

s such as sarin, which were developed as chemical weapons, 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, and other

terpene Terpenes () are a class of natural products consisting of compounds with the formula (C5H8)n for n ≥ 2. Terpenes are major biosynthetic building blocks. Comprising more than 30,000 compounds, these unsaturated hydrocarbons are produced predomi ...

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

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 provides ...

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 psychiatry, psychiatric treatment that causes a generalized seizure by passing electrical current through the brain. ECT is often used as an intervention for mental disorders when other treatments are inadequ ...

. Others such as strychnine and tetramethylenedisulfotetramine are used as rodenticides. Bemegride 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. Retrieved on September 20, 2014.

s (of barbiturates and

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...

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 and an agonist for kainate receptors 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 * DMCM * FG-7142 * Fipronil * Flumazenil * Flurothyl * Gabazine * IPTBO * Laudanosine * Oenanthotoxin * Pentylenetetrazol (

Metrazol Pentylenetetrazol (PTZ), also known as pentylenetetrazole, pentetrazol (International Nonproprietary Name, INN), and pentamethylenetetrazol, is a drug formerly used as a circulatory and respiratory stimulant. High doses cause convulsions, as dis ...

) * Phenylsilatrane * Picrotoxin * Sarmazenil * Securinine * Sinomenine * TBPO * TBPS * Tetramethylenedisulfotetramine * Thujone

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 * Colubrine * Diaboline * Gelsemine * Hyenandrine * Laudanosine * Oripavine * RU-5135 (also GABA antagonist) * Sinomenine * Strychnine * Thebaine * Tutin

Ionotropic glutamate receptor agonists

Ionotropic glutamate receptor agonists are drugs that activate the ionotropic glutamate receptors in the brain. * AMPA *

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 cont ...

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 * Quinolinic acid * Quisqualic acid * Tetrazolylglycine

Acetylcholine receptor agonists

Acetylcholine receptor agonists are drugs that activate the acetylcholine receptors. * Anatoxin-a * Pilocarpine

Advantages

Camphor injections for psychiatric treatment were inefficient and were replaced by pentylenetetrazol. 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 pentylenetetrazol 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 pentylenetetrazol-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