• Source: Convulsant

A convulsant is a drug which induces convulsions and/or epileptic seizures, the opposite of an anticonvulsant. These drugs generally act as stimulants at low doses, but are not used for this purpose due to the risk of convulsions and consequent excitotoxicity. Most convulsants are antagonists (or inverse agonists) at either the GABAA or glycine receptors, or ionotropic glutamate receptor agonists. 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 agents 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 terpenes given to children with colds can act as convulsants (sympathomimetics, piperazine derivatives, theophylline, antihistamines, etc.) in children who have had febrile seizures.




Uses


Some convulsants such as pentetrazol and flurothyl were previously used in shock therapy in psychiatric medicine, as an alternative to electroconvulsive therapy. Others such as strychnine and tetramethylenedisulfotetramine are used as poisons for exterminating pests. Bemegride and flumazenil are used to treat drug overdoses (of barbiturates and benzodiazepines 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 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






= GABAA receptor antagonists, inverse agonists or negative allosteric modulators

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

Bemegride
Bicuculline
Cicutoxin
Cyclothiazide
DMCM
FG-7142
Fipronil
Flumazenil
Flurothyl
Gabazine
IPTBO
Laudanosine
Oenanthotoxin
Pentylenetetrazol (Metrazol)
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
Kainic acid
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

Kata Kunci Pencarian:

• Enfluran
• Convulsant
• Trevor Dunn
• List of veterinary drugs
• MC-2973
• Pentylenetetrazol
• Anticonvulsant
• Phenobarbital
• Isoflurothyl
• CHEB
• Diberal