Aconvulsantis a drug which inducesconvulsionsand/orepileptic seizures,the opposite of ananticonvulsant.These drugs generally act asstimulantsat low doses, but are not used for this purpose due to the risk of convulsions and consequentexcitotoxicity.Most convulsants areantagonists(orinverse agonists) at either theGABAAorglycine receptors,orionotropicglutamate receptoragonists.[1]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.[2]Nerve agentssuch assarin,which were developed aschemical weapons,produce convulsions as a major part of theirtoxidrome,but also produce a number of other effects in the body and are usually classified separately.[3][4][5][6]Dieldrinwhich was developed as an insecticide blocks chloride influx into the neurons causing hyperexcitability of the CNS and convulsions.[7]The Irwin observation test and other studies that record clinical signs are used to test the potential for a drug to induce convulsions.[8]Camphor,and otherterpenesgiven to children with colds can act as convulsants (sympathomimetics,piperazinederivatives,theophylline,antihistamines,etc.) in children who have hadfebrile seizures.[9]
Uses
editSome convulsants such aspentetrazolandflurothylwere previously used inshock therapyin psychiatric medicine, as an alternative toelectroconvulsive therapy.[10]Others such asstrychnineandtetramethylenedisulfotetramineare used as poisons for exterminating pests.[11]Bemegrideandflumazenilare used to treat drugoverdoses(ofbarbituratesandbenzodiazepinesrespectively), but may cause convulsions if the dose is too high.[12][13]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.[14][15][16]For example,kainic acidcan lead to status epilepticus in animals as it is a cyclic analog ofl-glutamateand an agonist forkainate receptorsin the brain which makes it a potent neurotoxin and excitant.[17]
Examples
editGABAAreceptor antagonists, inverse agonists or negative allosteric modulators
editGABAAreceptor antagonistsare drugs that bind toGABAAreceptorsbut do not activate them and inhibit the action of GABA. Thus it blocks both the endogenous and exogenous actions of GABAAreceptor agonists.[18][19]
- 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
editGABA synthesis inhibitors are drugs that inhibit the action ofGABA.[20]
Glycine receptor antagonists
editGlycine receptor antagonistsare drugs which inactivates the glycine receptors.[21]
- Bicuculline
- Brucine
- Colubrine
- Diaboline
- Gelsemine
- Hyenandrine
- Laudanosine
- Oripavine
- RU-5135(also GABA antagonist)
- Sinomenine
- Strychnine
- Thebaine
- Tutin
Ionotropic glutamate receptor agonists
editIonotropic glutamate receptor agonists are drugs that activate theionotropic glutamate receptorsin the brain.[22]
Acetylcholine receptor agonists
editAcetylcholine receptor agonistsare drugs that activate the acetylcholine receptors.[23]
Advantages
editCamphorinjections for psychiatric treatment were inefficient and were replaced bypentylenetetrazol.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.[10]
Risks/Complications
editConvulsants likepentylenetetrazolandflurothylwere 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.[10]
History
editIn 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.[10]
References
edit- ^"Convulsant Agent - an overview | ScienceDirect Topics".www.sciencedirect.com.Retrieved2022-01-15.[vague]
- ^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.PMC4767205.PMID26174744.
- ^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.PMID15119942.S2CID28716793.
- ^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.PMID18615309.S2CID5081215.
- ^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.PMC3651659.PMID23425285.
- ^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.PMID23000013.
- ^"Dieldrin - an overview | ScienceDirect Topics".www.sciencedirect.com.Retrieved2022-01-20.[vague]
- ^"Convulsant Agent - an overview | ScienceDirect Topics".www.sciencedirect.com.Retrieved2022-01-20.[vague]
- ^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.PMID1363740.INIST3915621.
- ^abcdCooper, 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.PMID25029329.S2CID23735035.
- ^"Convulsant Agent - an overview | ScienceDirect Topics".www.sciencedirect.com.Retrieved2022-01-15.[vague]
- ^Kang, Michael; Galuska, Michael A.; Ghassemzadeh, Sassan (2024)."Benzodiazepine Toxicity".StatPearls.StatPearls Publishing.PMID29489152.
- ^Suddock, Jolee T.; Kent, Kristen J.; Cain, Matthew D. (2024)."Barbiturate Toxicity".StatPearls.StatPearls Publishing.PMID29763050.
- ^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.PMID12151122.S2CID5930079.
- ^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.PMID19292981.
- ^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.PMID20868357.
- ^"Kainic Acid - an overview | ScienceDirect Topics".www.sciencedirect.com.Retrieved2022-01-15.[vague]
- ^"GABA-A Receptor Antagonists".Medical Subject Headings.National Library of Medicine.Retrieved23 November2024.
- ^"GABAA Receptor Agonists - an overview | ScienceDirect Topics".www.sciencedirect.com.Retrieved2022-01-18.[vague]
- ^George, Kevin; Preuss, Charles V.; Sadiq, Nazia M. (2024)."GABA Inhibitors".StatPearls.StatPearls Publishing.PMID31424814.
- ^"Glycine Receptor Antagonist - an overview | ScienceDirect Topics".www.sciencedirect.com.Retrieved2022-01-18.[vague]
- ^Celli, Roberta; Fornai, Francesco (2021)."Targeting Ionotropic Glutamate Receptors in the Treatment of Epilepsy".Current Neuropharmacology.19(6): 747–765.doi:10.2174/1570159X18666200831154658.ISSN1875-6190.PMC8686308.PMID32867642.
- ^"Acetylcholine receptor anatomy".www.openanesthesia.org.Retrieved2022-01-18.