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Convulsant

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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.[citation needed] 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.[1] 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.[2][3][4][5] Dieldrin which was developed as an insecticide blocks chloride influx into the neurons causing hyperexcitability of the CNS and convulsions.[citation needed] The Irwin observation test and other studies that record clinical signs are used to test the potential for a drug to induce convulsions.[citation needed] 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.[6]

Uses

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Some convulsants such as pentetrazol and flurothyl were previously used in shock therapy in psychiatric medicine, as an alternative to electroconvulsive therapy.[7] Others such as strychnine and tetramethylenedisulfotetramine are used as poisons for exterminating pests.[citation needed] Bemegride and flumazenil are used to treat drug overdoses (of barbiturates and benzodiazepines respectively), but may cause convulsions if the dose is too high.[8][9] 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.[10][11][12] 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.[citation needed]

Examples

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GABAA receptor antagonists, inverse agonists or negative allosteric modulators

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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.[13]

GABA synthesis inhibitors

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GABA synthesis inhibitors are drugs that inhibit the action of GABA.[14]

Glycine receptor antagonists

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Glycine receptor antagonists are drugs which inactivates the glycine receptors.[citation needed]

Ionotropic glutamate receptor agonists

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Ionotropic glutamate receptor agonists are drugs that activate the ionotropic glutamate receptors in the brain.[15]

Acetylcholine receptor agonists

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Acetylcholine receptor agonists are drugs that activate the acetylcholine receptors.[16]

Advantages

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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.[7]

Risks/Complications

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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.[7]

History

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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.[7]

References

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  1. ^ Chen, Hsien-Yi; Albertson, Timothy E.; Olson, Kent R. (March 2016). "Treatment of drug-induced seizures: Treatment of drug-induced seizures". British Journal of Clinical Pharmacology. 81 (3): 412–419. doi:10.1111/bcp.12720. PMC 4767205. PMID 26174744.
  2. ^ Mares P, Folbergrová J, Kubová H (2004). "Excitatory aminoacids and epileptic seizures in immature brain". Physiological Research. 53 (Suppl 1): S115-24. doi:10.33549/physiolres.930000.53.S115. PMID 15119942. S2CID 28716793.
  3. ^ Calabrese EJ (2008). "Modulation of the epileptic seizure threshold: implications of biphasic dose responses". Critical Reviews in Toxicology. 38 (6): 543–56. doi:10.1080/10408440802014261. PMID 18615309. S2CID 5081215.
  4. ^ Johnston GA (May 2013). "Advantages of an antagonist: bicuculline and other GABA antagonists". British Journal of Pharmacology. 169 (2): 328–36. doi:10.1111/bph.12127. PMC 3651659. PMID 23425285.
  5. ^ de Araujo Furtado M, Rossetti F, Chanda S, Yourick D (December 2012). "Exposure to nerve agents: from status epilepticus to neuroinflammation, brain damage, neurogenesis and epilepsy". Neurotoxicology. 33 (6): 1476–1490. doi:10.1016/j.neuro.2012.09.001. PMID 23000013.
  6. ^ Galland, M. C.; Griguer, Y.; Morange-Sala, S.; Jean-Pastor, M. J.; Rodor, F.; Jouglard, J. (1992). "Convulsions fébriles : faut-il contre-indiquer certains médicaments ?" [Febrile convulsions: should some drugs be contraindicated?]. Thérapie (in French). 47 (5): 409–414. PMID 1363740. INIST 3915621.
  7. ^ a b c d Cooper, Kathryn; Fink, Max (October 2014). "The Chemical Induction of Seizures in Psychiatric Therapy: Were Flurothyl (Indoklon) and Pentylenetetrazol (Metrazol) Abandoned Prematurely?". Journal of Clinical Psychopharmacology. 34 (5): 602–607. doi:10.1097/JCP.0000000000000173. PMID 25029329. S2CID 23735035.
  8. ^ Kang, Michael; Galuska, Michael A.; Ghassemzadeh, Sassan (2024). "Benzodiazepine Toxicity". StatPearls. StatPearls Publishing. PMID 29489152.
  9. ^ Suddock, Jolee T.; Kent, Kristen J.; Cain, Matthew D. (2024). "Barbiturate Toxicity". StatPearls. StatPearls Publishing. PMID 29763050.
  10. ^ Löscher W (June 2002). "Animal models of epilepsy for the development of antiepileptogenic and disease-modifying drugs. A comparison of the pharmacology of kindling and post-status epilepticus models of temporal lobe epilepsy". Epilepsy Research. 50 (1–2): 105–23. doi:10.1016/s0920-1211(02)00073-6. PMID 12151122. S2CID 5930079.
  11. ^ Löscher W (May 2009). "Preclinical assessment of proconvulsant drug activity and its relevance for predicting adverse events in humans". European Journal of Pharmacology. 610 (1–3): 1–11. doi:10.1016/j.ejphar.2009.03.025. PMID 19292981.
  12. ^ Rubio C, Rubio-Osornio M, Retana-Márquez S, Verónica Custodio ML, Paz C (December 2010). "In vivo experimental models of epilepsy". Central Nervous System Agents in Medicinal Chemistry. 10 (4): 298–309. doi:10.2174/187152410793429746. PMID 20868357.
  13. ^ "GABA-A Receptor Antagonists". Medical Subject Headings. National Library of Medicine. Retrieved 28 December 2024.
  14. ^ George, Kevin; Preuss, Charles V.; Sadiq, Nazia M. (2024). "GABA Inhibitors". StatPearls. StatPearls Publishing. PMID 31424814.
  15. ^ Celli, Roberta; Fornai, Francesco (2021). "Targeting Ionotropic Glutamate Receptors in the Treatment of Epilepsy". Current Neuropharmacology. 19 (6): 747–765. doi:10.2174/1570159X18666200831154658. ISSN 1875-6190. PMC 8686308. PMID 32867642.
  16. ^ "Acetylcholine receptor anatomy". www.openanesthesia.org. Retrieved 2022-01-18.
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