View source for Strychnine

{{Short description|Poisonous substance used as pesticide}}
{{CS1 config|name-list-style=vanc|display-authors=6}}
{{For|the song by The Sonics|Here Are the Sonics}}
{{Chembox
| Watchedfields  = changed
| verifiedrevid  = 470471685
| ImageFile      = Strychnine.svg
| ImageClass     = skin-invert-image
| ImageSize      = 180
| ImageFile1     = Strychnine-from-xtal-3D-balls.png
| IUPACName      = Strychnidin-10-one<ref>Retrieved from SciFinder. [May 7, 2018]</ref>
| SystematicName = (4b''R'',4b<sup>1</sup>''S'',7a''S'',8a''R'',8a<sup>1</sup>''R'',12a''S'')-4b<sup>1</sup>,5,6,7a,8,8a,8a<sup>1</sup>,11,12a,13-Decahydro-14''H''-12-oxa-7,14a-diaza-7,9-methanocyclohepta[''cd'']cyclopenta[''g'']fluoranthen-14-one
| OtherNames     =

| Section1 = {{Chembox Identifiers
| IUPHAR_ligand    = 347
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID     = 389877
| UNII_Ref         = {{fdacite|correct|FDA}}
| UNII             = H9Y79VD43J
| UNII_Comment     = (base)
| UNII1_Ref        = {{fdacite|correct|FDA}}
| UNII1            = FA486DV76S
| UNII1_Comment    = (sulfate)
| InChI            = 1/C21H22N2O2/c24-18-10-16-19-13-9-17-21(6-7-22(17)11-12(13)5-8-25-16)14-3-1-2-4-15(14)23(18)20(19)21/h1-5,13,16-17,19-20H,6-11H2/t13-,16-,17-,19-,20-,21+/m0/s1
| InChIKey         = QMGVPVSNSZLJIA-FVWCLLPLBR
| StdInChI_Ref     = {{stdinchicite|correct|chemspider}}
| StdInChI         = 1S/C21H22N2O2/c24-18-10-16-19-13-9-17-21(6-7-22(17)11-12(13)5-8-25-16)14-3-1-2-4-15(14)23(18)20(19)21/h1-5,13,16-17,19-20H,6-11H2/t13-,16-,17-,19-,20-,21+/m0/s1
| StdInChIKey_Ref  = {{stdinchicite|correct|chemspider}}
| StdInChIKey      = QMGVPVSNSZLJIA-FVWCLLPLSA-N
| CASNo_Ref        = {{cascite|correct|CAS}}
| CASNo            = 57-24-9
| CASNo_Comment    = (base)
| CASNo1_Ref       = {{cascite|correct|CAS}}
| CASNo1           = 60-41-3
| CASNo1_Comment   = (sulfate)
| PubChem          = 441071
| ChEMBL_Ref       = {{ebicite|correct|EBI}}
| ChEMBL           = 227934
| ChEMBL2_Ref      = {{ebicite|correct|EBI}}
| ChEMBL2          = 612118
| ChEMBL3_Ref      = {{ebicite|correct|EBI}}
| ChEMBL3          = 486399
| KEGG_Ref         = {{keggcite|correct|kegg}}
| KEGG             = C06522
| ChEBI_Ref        = {{ebicite|correct|EBI}}
| ChEBI            = 28973
| SMILES           = O=C7N2c1ccccc1[C@@]64[C@@H]2[C@@H]3[C@@H](OC/C=C5\[C@@H]3C[C@@H]6N(CC4)C5)C7
| RTECS            = WL2275000
| UNNumber         = 1692
}}

| Section2 = {{Chembox Properties
| C=21 | H=22 | N=2 | O=2
| Odor       = Odorless
| Appearance = White or translucent crystal or crystalline powder; Bitter tasting
| Density    = 1.36 g cm<sup>−3</sup>
| BoilingPtK = 557 to 559
| MeltingPtK = 543
| pKa        = 8.25<ref name="Everett1957">{{cite journal | doi = 10.1039/JR9570001120 | title = The constitution of aspidospermine. Part III. Reactivity at the nitrogen atoms, and biogenetic considerations | journal = Journal of the Chemical Society | pages = 1120–1123 | year = 1957 | vauthors = Everett AJ, Openshaw HT, Smith GF | s2cid = 94111547}}</ref>
| Solubility = 0.02% (20°C)<ref name="PGCH" />
}}

| Section3 = {{Chembox Pharmacology
| Legal_AU         = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| Legal_BR         = F4
| Legal_BR_comment = <ref>{{cite web | author = Anvisa | author-link = Brazilian Health Regulatory Agency | date = 2023-07-24 | title = RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial | trans-title = Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control | url = https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 | url-status = live | archive-url = https://web.archive.org/web/20230827163149/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 | archive-date = 2023-08-27 | access-date = 2023-08-27 | publisher = [[Diário Oficial da União]] | language = pt-BR | publication-date = 2023-07-25}}</ref>
| Legal_CA         = <!-- Unscheduled / Schedule I, II, III, IV, V, VI, VII, VIII -->
| Legal_DE         = <!-- Anlage I, II, III or Unscheduled -->
| Legal_NZ         = <!-- Class A, B, C -->
| Legal_UK         = <!-- GSL / P / POM / CD / Class A, B, C -->
| Legal_US         = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| Legal_UN         = <!-- N I, II, III, IV / P I, II, III, IV -->
| Legal_EU         =
| Legal_status     =
}}

| Section4 = {{Chembox Hazards
| MainHazards    = Extremely toxic
| GHSPictograms  = {{GHS06}}{{GHS09}}
| GHSSignalWord  = Danger
| HPhrases       = {{H-phrases|300|310|330|410}}
| PPhrases       = {{P-phrases|260|264|273|280|284|301+310}}
| NFPA-H         = 4
| NFPA-F         = 0
| NFPA-R         = 0
| FlashPt        = Non flammable
| AutoignitionPt = Non flammable
| IDLH           = 3 mg/m<sup>3</sup><ref name="PGCH" />
| PEL            = TWA 0.15 mg/m<sup>3</sup><ref name="PGCH" />
| REL            = TWA 0.15 mg/m<sup>3</sup><ref name="PGCH" />
| LD50           = {{ubl|0.5 mg/kg (dog, oral)|0.5 mg/kg (cat, oral)|2 mg/kg (mouse, oral)|16 mg/kg (rat, oral)|2.35 mg/kg (rat, oral)<ref name="IDLH">{{IDLH|57249|Strychnine}}</ref>}}
| LDLo           = 0.6 mg/kg (rabbit, oral)<ref name="IDLH" />
}}
}}<!-- end Template:Chembox -->

'''Strychnine''' ({{IPAc-en|ˈ|s|t|r|ɪ|k|n|iː|n|,_|-|n|ɪ|n}}, {{respell|STRIK|neen|,_-|nin}}, <small>[[American English|US]] chiefly</small> {{IPAc-en|-|n|aɪ|n}} {{respell|-|nyne}})<ref>{{cite LPD|3}}</ref><ref>{{cite EPD|18}}</ref> is a highly [[toxicity|toxic]], colorless, bitter, [[crystal]]line [[alkaloid]] used as a [[pesticide]], particularly for killing small [[vertebrate]]s such as [[bird]]s and [[rodent]]s. Strychnine, when inhaled, swallowed, or absorbed through the eyes or mouth, causes [[Strychnine poisoning|poisoning]] which results in muscular [[convulsion]]s and eventually death through [[asphyxia]].<ref name="sharma">{{cite book | vauthors = Sharma RK | year = 2007 | chapter = Spinal Poisons | title = Concise Textbook of Forensic Medicine & Toxicology | language = en | edition = 2nd | publisher = Elsevier | pages = 306–308 | isbn = 978-81-312-1145-8}}</ref> While it is no longer used medicinally, it was used historically in small doses to strengthen muscle contractions, such as a heart<ref>{{cite news |title=Dead from Strychnine Overdose |url=https://www.newspapers.com/image/876944834/?match=1&terms=strychnine%20overdose |access-date=24 June 2024 |publisher=[[Newark Star-Eagle]] |date=12 July 1915}}</ref> and bowel stimulant<ref>{{cite journal | last = Munro | first = JMH | title = Veronal Poisoning: Case of Recovery from 125 Grains | date = 1914-04-18 | journal = British Medical Journal | volume = 1 | issue = 2781 | pages = 854–856 | doi = 10.1136/bmj.1.2781.854 | issn = 0007-1447 | pmc = 2300683 | pmid = 20767090 | s2cid = 41592291 | quote = An attempt was made to administer a soap-and-water enema, but the sphincter was not acting. After hypodermic injection of 1/45 grain [1.44 mg] strychnine, a second attempt was made, and a good evacuation of the bowel followed, after which half a pint [284 ml] of normal saline was injected and retained. [...] We decided to adhere to the treatment already commenced – namely, periodical rectal injection of saline and withdrawals of urine by catheter, with oxygen inhalation for cyanosis, and strychnine hypodermically as the pulse weakened.}}</ref> and performance-enhancing drug. The most common source is from the seeds of the ''[[Strychnos nux-vomica]]'' tree.

== Biosynthesis ==
[[File:StrychnineIII.svg|class=skin-invert-image|left|350px|Strychnine biosynthesis]]

Strychnine is a [[terpene]] [[indole]] [[alkaloid]] belonging to the ''[[Strychnos]]'' family of ''[[Corynanthe]]'' alkaloids, and it is derived from [[tryptamine]] and [[secologanin]].<ref name="Bonjoch 3455–3482">{{cite journal | vauthors = Bonjoch J, Solé D | title = Synthesis of Strychnine | journal = Chemical Reviews | volume = 100 | issue = 9 | pages = 3455–3482 | date = September 2000 | pmid = 11777429 | doi = 10.1021/cr9902547 | s2cid = 30921537}}</ref><ref>{{cite book | vauthors = Dewick PM | title = Medicinal natural products: a biosynthetic approach | year = 2009 | publisher = A John Wiley & Sons | location = Chichester | isbn = 978-0-470-74167-2 | pages = 377–378 | edition = 3rd}}</ref> The biosynthesis of strychnine was solved in 2022.<ref>{{cite journal | doi = 10.1038/s41586-022-04950-4 | title = Biosynthesis of strychnine | journal = Nature | date = July 2022 | volume = 607 | issue = 7919 | pages = 617–622 | last1 = Hong | first1 = Benke | last2 = Grzech | first2 = Dagny | last3 = Caputi | first3 = Lorenzo | last4 = Sonawane | first4 = Prashant | last5 = López | first5 = Carlos E. Rodríguez | last6 = Kamileen | first6 = Mohamed Omar | last7 = Hernández Lozada | first7 = Néstor J. | last8 = Grabe | first8 = Veit | last9 = O'Connor | first9 = Sarah E. | pmid = 35794473 | pmc = 9300463 | s2cid = 250337382 | bibcode = 2022Natur.607..617H}}</ref> The enzyme, [[strictosidine synthase]], catalyzes the condensation of tryptamine and secologanin, followed by a [[Pictet-Spengler reaction]] to form [[strictosidine]].<ref>{{cite journal | vauthors = Treimer JF, Zenk MH | title = Purification and properties of strictosidine synthase, the key enzyme in indole alkaloid formation | journal = European Journal of Biochemistry | volume = 101 | issue = 1 | pages = 225–233 | date = November 1979 | pmid = 510306 | s2cid = 44588157 | doi = 10.1111/j.1432-1033.1979.tb04235.x | doi-access = free}}</ref> Many steps have been inferred by isolation of intermediates from ''Strychnos nux-vomica''.<ref name="Heimberger 217">{{cite journal | doi = 10.1039/C39730000217 | title = Biosynthesis of strychnine | journal = Journal of the Chemical Society, Chemical Communications | issue = 6 | pages = 217–218 | year = 1973 | vauthors = Heimberger SI, Scott AI | s2cid = 98685777}}</ref> The next step is hydrolysis of the [[acetal]], which opens the ring by elimination of [[glucose]] (O-Glu) and provides a reactive aldehyde. The nascent aldehyde is then attacked by a secondary amine to afford [[geissoschizine]], a common intermediate of many related compounds in the ''Strychnos'' family.<ref name="Bonjoch 3455–3482" />

A reverse Pictet-Spengler reaction cleaves the C2–C3 bond, while subsequently forming the C3–C7 bond via a 1,2-alkyl migration, an oxidation from a [[Cytochrome P450]] enzyme to a spiro-[[oxindole]], nucleophilic attack from the [[enol]] at C16, and elimination of oxygen forms the C2–C16 bond to provide [[dehydropreakuammicine]].<ref>{{cite journal | vauthors = Tatsis EC, Carqueijeiro I, Dugé de Bernonville T, Franke J, Dang TT, Oudin A, Lanoue A, Lafontaine F, Stavrinides AK, Clastre M, Courdavault V, O'Connor SE | title = A three enzyme system to generate the Strychnos alkaloid scaffold from a central biosynthetic intermediate | journal = Nature Communications | volume = 8 | issue = 1 | article-number = 316 | date = August 2017 | pmid = 28827772 | pmc = 5566405 | doi = 10.1038/s41467-017-00154-x | doi-access = free | bibcode = 2017NatCo...8..316T | s2cid = 205542422}}</ref> Hydrolysis of the methyl ester and [[decarboxylation]] leads to [[norfluorocurarine]]. Stereospecific reduction of the endocyclic double bond by [[NADPH]] and [[hydroxylation]] provides the [[Wieland-Gumlich aldehyde]], which was first isolated by Heimberger and Scott in 1973, although previously synthesized by Wieland and Gumlich in 1932.<ref name="Heimberger 217" /><ref>{{cite journal | doi = 10.1002/jlac.19324940116 | title = Über einige neue Reaktionen der Strychnos – Alkaloide. XI | trans-title = On some new reactions of the Strychnos alkaloids. XI | language = de | journal = Justus Liebig's Annalen der Chemie | volume = 494 | pages = 191–200 | year = 1932 | vauthors = Wieland H, Gumlich W | s2cid = 95378554}}</ref> To elongate the appendage by two carbons, [[acetyl-CoA]] is added to the aldehyde in an [[aldol reaction]] to afford prestrychnine. Strychnine is then formed by a facile addition of the amine with the [[carboxylic acid]] or its activated CoA [[thioester]], followed by ring-closure via displacement of an activated alcohol.

== Chemical synthesis ==
{{Main|Strychnine total synthesis}}

As early researchers noted, the strychnine molecular structure, with its specific array of [[Ring (chemistry)|rings]], [[stereocenter]]s, and nitrogen [[functional group]]s, is a complex synthetic target, and has stimulated interest for that reason and for interest in the [[structure–activity relationship]]s underlying its pharmacologic activities.<ref>{{cite journal | vauthors = Nicolaou KC, Vourloumis D, Winssinger N, Baran PS | title = The Art and Science of Total Synthesis at the Dawn of the Twenty-First Century | journal = Angewandte Chemie | volume = 39 | issue = 1 | pages = 44–122 | date = January 2000 | pmid = 10649349 | doi = 10.1002/(SICI)1521-3773(20000103)39:1<44::AID-ANIE44>3.0.CO;2-L | s2cid = 20559096}}</ref> An early synthetic chemist targeting strychnine, [[Robert Burns Woodward]], quoted the chemist who determined its structure through chemical decomposition and related physical studies as saying that "for its molecular size it is the most complex organic substance known" (attributed to [[Robert Robinson (organic chemist)|Sir Robert Robinson]]).<ref>{{cite journal | vauthors = Robinson R | year = 1952 | title = Molecular structure of Strychnine, Brucine and Vomicine | journal = Progress in Organic Chemistry | volume = 1 | page = 2}}</ref><ref>{{cite journal | vauthors = Seeman JI, House MC | author-link1 = Jeffrey I. Seeman | year = 2022 | title = 'For Its Size, the Most Complex Natural Product Known.' Who Deserves Credit for Determining the Structure of Strychnine? | journal = [[ACS Central Science]] | volume = 8 | issue = 6 | pages = 672–681 | doi = 10.1021/acscentsci.1c01348 | pmc = 9228570 | pmid = 35756373 | quote = For its molecular size it is the most complex substance known.}} citing {{cite journal | vauthors = Woodward RB, Cava MP, Ollis WD, Hunger A, Daeniker HU, Schenker K | year = 1963 | title = The Total Synthesis of Strychnine | journal = [[Tetrahedron (journal)|Tetrahedron]] | volume = 19 | issue = 2 | pages = 247–288 | doi = 10.1016/S0040-4020(01)98529-1}}</ref>

[[File:Strychnine Star chemdraw.jpg|class=skin-invert-image|300px|left]]

The first [[total synthesis]] of strychnine was reported by the research group of R. B. Woodward in 1954, and is considered a classic in this field.<ref>{{cite book | vauthors = Nicolaou KC, Sorensen EJ | date = 1996 | title = Classics in Total Synthesis: Targets, Strategies, Methods | publisher = Wiley | isbn = 978-3-527-29231-8}} {{page needed|date=June 2014}}</ref><ref name="Bonjoch 3455–3482" /> The Woodward account published in 1954 was very brief (3 pages),<ref>{{cite journal | vauthors = Woodward RB, Cava MP, Ollis WD, Hunger A, Daeniker HU, Schenker K | title = The total synthesis of strychnine | journal = Journal of the American Chemical Society | volume = 76 | issue = 18 | pages = 4749–4751 | year = 1954 | doi = 10.1021/ja01647a088| bibcode = 1954JAChS..76.4749W }}</ref> but was followed by a 42-page report in 1963.<ref>{{cite journal | vauthors = Woodward RB | title = The total synthesis of strychnine | journal = Experientia | volume = 19 | issue = Suppl 2 | pages = 213–228 | year = 1963 | pmid = 13305562 | doi = 10.1016/S0040-4020(01)98529-1}}</ref> The molecule has since received continuing wide attention in the years since for the challenges to synthetic organic strategy and tactics presented by its complexity; its synthesis has been targeted and its stereocontrolled preparation independently achieved by more than a dozen research groups since the first success.<ref>{{cite journal | last1 = Eichberg | first1 = Michael J. | last2 = Dorta | first2 = Rosa L. | last3 = Lamottke | first3 = Kai | last4 = Vollhardt | first4 = K. Peter C. | year = 2000 | title = The Formal Total Synthesis of (±)-Strychnine via a Cobalt-Mediated [2 + 2 + 2]Cycloaddition | journal = [[Org. Lett.]] | volume = 2 | issue = 16| pages = 2479–2481 | doi = 10.1021/ol006131m | pmid = 10956526 }}</ref><ref>{{cite journal | last1 = Eichberg | first1 = Michael J. | last2 = Dorta | first2 = Rosa L. | last3 = Grotjahn | first3 = Douglas B. | last4 = Lamottke | first4 = Kai | last5 = Schmidt | first5 = Martin | last6 = Vollhardt | first6 = K. Peter C. | year = 2001 | title = Approaches to the Synthesis of (±)-Strychnine via the Cobalt-Mediated [2 + 2 + 2] Cycloaddition: Rapid Assembly of a Classic Framework | journal = [[J. Am. Chem. Soc.]] | volume = 123 | issue = 38| pages = 9324–9337 | doi = 10.1021/ja016333t | pmid = 11562215 | bibcode = 2001JAChS.123.9324E }}</ref>

== Mechanism of action ==
Strychnine is a [[neurotoxin]] which acts as an [[receptor antagonist|antagonist]] of [[glycine receptor|glycine]] and [[acetylcholine receptor]]s. It primarily affects the motor nerve fibers in the spinal cord which control muscle contraction. An impulse is triggered at one end of a nerve cell by the binding of [[neurotransmitter]]s to the receptors. In the presence of an inhibitory neurotransmitter, such as [[glycine]], a greater quantity of excitatory neurotransmitters must bind to receptors before an [[action potential]] is generated. Glycine acts primarily as an agonist of the glycine receptor, which is a [[Ligand-gated ion channel|ligand-gated]] chloride channel in neurons located in the spinal cord and in the brain. This [[chloride channel]] allows the negatively charged chloride ions into the neuron, causing a [[Hyperpolarization (biology)|hyperpolarization]] which pushes the membrane potential further from threshold. Strychnine is an antagonist of glycine; it binds noncovalently to the same receptor, preventing the inhibitory effects of glycine on the postsynaptic neuron. Therefore, action potentials are triggered with lower levels of excitatory neurotransmitters. When the inhibitory signals are prevented, the motor neurons are more easily activated and the victim has spastic muscle contractions, resulting in death by asphyxiation.<ref name="sharma" /><ref>{{cite book | vauthors = Waring RH, Steventon GB, Mitchell SC | title = Molecules of death | publisher = Imperial College Press | date = 2007}} {{page needed|date=February 2017}}</ref> Strychnine binds the ''[[Aplysia californica]]'' acetylcholine binding protein (a homolog of [[nicotinic acetylcholine receptor|nicotinic receptors]]) with high affinity but low specificity, and does so in multiple conformations.<ref name="Brams2011">{{cite journal | vauthors = Brams M, Pandya A, Kuzmin D, van Elk R, Krijnen L, Yakel JL, Tsetlin V, Smit AB, Ulens C | title = A structural and mutagenic blueprint for molecular recognition of strychnine and d-tubocurarine by different cys-loop receptors | journal = PLOS Biology | volume = 9 | issue = 3 | article-number = e1001034 | date = March 2011 | pmid = 21468359 | pmc = 3066128 | doi = 10.1371/journal.pbio.1001034 | doi-access = free | s2cid = 14123035}}</ref>

== Toxicity ==
{{main|Strychnine poisoning}}
In high doses, strychnine is very toxic to humans (minimum lethal oral dose in adults is 30–120&nbsp;mg) and many other animals (oral {{LD50}} = 16&nbsp;mg/kg in rats, 2&nbsp;mg/kg in mice),<ref>{{cite web | work = INCHEM: Chemical Safety Information from Intergovernmental Organizations | title = Strychnine | url = http://www.inchem.org/documents/pims/chemical/pim507.htm | access-date = 2010-12-14 | archive-date = 2015-01-03 | archive-url = https://web.archive.org/web/20150103231725/http://www.inchem.org/documents/pims/chemical/pim507.htm | url-status = live}}</ref> and poisoning by inhalation, swallowing, or absorption through eyes or mouth can be fatal. ''S. nux-vomica'' seeds are generally effective as a poison only when they are crushed or chewed before swallowing because the [[pericarp]] is quite hard and indigestible; poisoning symptoms may therefore not appear if the seeds are ingested whole.<ref name="pmid21823220">{{cite journal | vauthors = Koleva II, van Beek TA, Soffers AE, Dusemund B, Rietjens IM | title = Alkaloids in the human food chain--natural occurrence and possible adverse effects | journal = Molecular Nutrition & Food Research | volume = 56 | issue = 1 | pages = 30–52 | date = January 2012 | pmid = 21823220 | doi = 10.1002/mnfr.201100165 | s2cid = 9188046}}</ref><ref name="pmid29083795">{{cite book | pmid = 29083795 | id = {{NCBIBook|NBK459306}} | title = Strychnine Toxicity | publisher = StatPearls | vauthors = Otter J, D'Orazio JL | date = August 7, 2023}}</ref>

=== Animal toxicity ===
[[File:Paolucci & lupi.jpg|left|thumb|Wolves poisoned with strychnine in [[Abruzzo National Park]], Italy, 1924.]]
Strychnine poisoning in animals usually occurs from ingestion of baits designed for use against gophers, rats, squirrels, moles, chipmunks and coyotes. Strychnine is also used as a [[rodenticide]], but is not specific to such unwanted pests and may kill other small animals.<ref>{{cite news |title=Sale of free strychnine, an outrageous abuse of the County's liberal policy |url=https://www.newspapers.com/image/565833577/?match=1&terms=strychnine%20abuse |access-date=5 June 2024 |publisher=The Weekly Spokesman-Review |date=23 August 1894}}</ref><ref name="CDC_card">{{cite web | title = CDC – The Emergency Response Safety and Health Database: Biotoxin: Strychnine – NIOSH | url = https://www.cdc.gov/niosh/ershdb/emergencyresponsecard_29750018.html | website = www.cdc.gov | access-date = 2016-01-02 | archive-date = 2015-12-21 | archive-url = https://web.archive.org/web/20151221180423/http://www.cdc.gov/niosh/ershdb/emergencyresponsecard_29750018.html | url-status = live}}</ref> In the United States, most baits containing strychnine have been replaced with [[zinc phosphide]] baits since 1990. In the European Union, rodenticides with strychnine have been forbidden since 2006. Some animals are immune to strychnine; usually these have evolved resistance to poisonous [[strychnos alkaloids]] in the fruit they eat, such as [[Megabats|fruit bats]]. The [[drugstore beetle]] has a symbiotic gut yeast that allows it to digest pure strychnine.

Strychnine toxicity in rats is dependent on sex. It is more toxic to females than to males when administered via [[subcutaneous injection]] or [[intraperitoneal injection]]. Differences are due to higher rates of metabolism by male rat liver microsomes. Dogs and cats are more susceptible among domestic animals, pigs are believed to be as susceptible as dogs, and horses are able to tolerate relatively large amounts of strychnine. Birds affected by strychnine poisoning exhibit wing droop, [[salivation]], [[tremor]]s, muscle tenseness, and [[convulsions]]. Death occurs as a result of [[respiratory arrest]]. The clinical signs of strychnine poisoning relate to its effects on the [[central nervous system]]. The first clinical signs of poisoning include nervousness, restlessness, twitching of the muscles, and stiffness of the neck. As the poisoning progresses, the muscular twitching becomes more pronounced and convulsions suddenly appear in all the skeletal muscles. The limbs are extended and the neck is curved to [[opisthotonus]]. The pupils are widely dilated. As death approaches, the convulsions follow one another with increased rapidity, severity, and duration. Death results from asphyxia due to prolonged paralysis of the respiratory muscles. Following the ingestion of strychnine, symptoms of poisoning usually appear within 15 to 60 minutes.

{| class="wikitable sortable" style="margin-left:auto; margin-right:auto;"
|+ The {{LD50}} values for strychnine in animals
|-
! scope="col" | Organism
! scope="col" | Route
! scope="col" | LD<sub>50</sub> (mg/kg)
! scope="col" class="unsortable" | Ref.
|-
| Bird (wild)
| Oral
| 16
| <ref name="tucker">{{cite journal | vauthors = Tucker RK, Haegele MA | title = Comparative acute oral toxicity of pesticides to six species of birds | journal = Toxicology and Applied Pharmacology | volume = 20 | issue = 1 | pages = 57–65 | date = September 1971 | pmid = 5110827 | doi = 10.1016/0041-008X(71)90088-3 | bibcode = 1971ToxAP..20...57T | s2cid = 41296708}}</ref>
|-
| Cat
| Intravenous
| 0.33
| <ref name="rtecs">RTECS (1935)</ref>
|-
| Cat
| Oral
| 0.5
| <ref name="moraillon">{{cite journal | vauthors = Moraillon R, Pinoult L | title = Diagnostic et traitement d'intoxications courantes des carnivores | trans-title = Diagnosis and treatment of common poisoning of carnivores | year = 1978 | journal = Rec Med Vet | language = fr | volume = 174 | issue = 1–2 | pages = 36–43}}</ref>
|-
| Dog
| Intravenous
| 0.8
| <ref name="longo">{{cite journal | vauthors = Longo VG, Silvestrini B, Bovet D | title = An investigation of convulsant properties of the 5-7-diphenyl-1-3-diazadamantan-6-01 (1757-I. S.) | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 126 | issue = 1 | pages = 41–49 | date = May 1959 | doi = 10.1016/S0022-3565(25)25593-8 | pmid = 13642285 | s2cid = 41814802 | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=13642285 | access-date = 2017-02-05 | archive-date = 2020-03-26 | archive-url = https://web.archive.org/web/20200326144718/http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=13642285 | url-status = live| url-access = subscription }}</ref>
|-
| Dog
| Subcutaneous
| 0.35
| <ref name="rtecs" />
|-
| Dog
| Oral
| 0.5
| <ref name="moraillon" />
|-
| Duck
| Oral
| 3.0
| <ref name="tucker" />
|-
| Mouse
| Intraperitoneal
| 0.98
| <ref>{{cite journal | vauthors = Setnikar I, Murmann W, Magistretti MJ, Da Re P | title = Amino-methylchromones, brain stem stimulants and pentobarbital antagonists | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 128 | issue = 2 | pages = 176–181 | date = February 1960 | doi = 10.1016/S0022-3565(25)25736-6 | pmid = 14445192 | s2cid = 33238862 | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=14445192 | access-date = 2017-02-05 | archive-date = 2020-03-26 | archive-url = https://web.archive.org/web/20200326144720/http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=14445192 | url-status = live| url-access = subscription }}</ref>
|-
| Mouse
| Intravenous
| 0.41
| <ref>{{cite journal | vauthors = Haas H | title = [On 3-piperidino-1-phenyl-1-bicycloheptenyl-1-propanol (Akineton). 2] | journal = Archives Internationales de Pharmacodynamie et de Therapie | language = de | volume = 128 | pages = 204–238 | date = October 1960 | pmid = 13710192 | s2cid = 23479593}}</ref>
|-
| Mouse
| Oral
| 2.0
| <ref>{{cite journal | vauthors = Prasad CR, Patnaik GK, Gupta RC, Anand N, Dhawan BN | title = Central nervous system stimulant activity of n-(delta 3-chromene-3-carbonyl)-4 iminopyridine (compound 69/224) | journal = Indian Journal of Experimental Biology | volume = 19 | issue = 11 | pages = 1075–1076 | date = November 1981 | pmid = 7338366}}</ref>
|-
| Mouse
| Parenteral
| 1.06
| <ref>{{cite journal | vauthors = Zapata-Ortiz V, Castro De La Mata R, Barantes-Campos R | title = [The anticonvulsive action of cocaine] | language = de | journal = Arzneimittel-Forschung | volume = 11 | pages = 657–662 | date = July 1961 | pmid = 13787891 | trans-title = The anticonvulsive action of cocaine | author2-link = Ramiro Castro de la Mata | s2cid = 43797281}}</ref>
|-
| Mouse
| Subcutaneous
| 0.47
| <ref>{{cite journal | vauthors = Sandberg F, Kristianson K | title = A comparative study of the convulsant effects of strychnos alkaloids | journal = Acta Pharmaceutica Suecica | volume = 7 | issue = 4 | pages = 329–336 | date = September 1970 | pmid = 5480076 | s2cid = 28220152}}</ref>
|-
| Pigeon
| Oral
| 21.0
| <ref name="tucker" />
|-
| Quail
| Oral
| 23.0
| <ref name="tucker" />
|-
| Rabbit
| Intravenous
| 0.4
| <ref name="longo" />
|-
| Rabbit
| Oral
| 0.6
| <ref name="rtecs" />
|-
| Rat
| Oral
| 16.0
| <ref>{{cite book | vauthors = Spector WS | date = 1956 | title = Handbook of Toxicology | volume = 1 | page = 286 | publisher = W. B. Saunders Company | location = Philadelphia}}</ref>
|-
| Rat
| Intravenous
| 2.35
| <ref>{{cite journal | doi = 10.1002/jps.3030310406 | title = Strychnine X. Comparative accuracies of stomach tube and intraperitoneal injection methods of bioassay | journal = Journal of the American Pharmaceutical Association | volume = 31 | issue = 4 | pages = 113–115 | year = 1942 | vauthors = Ward JC, Crabtree DG}}</ref>
|}

=== Human toxicity ===
[[File:Opisthotonus in a patient suffering from tetanus - Painting by Sir Charles Bell - 1809.jpg|thumb|An 1809 painting by [[Charles Bell]] depicting opisthotonus caused by tetanus]]

After injection, inhalation, or ingestion, the first symptoms to appear are generalized [[Spasm|muscle spasms]]. They appear very quickly after inhalation or injection – within as few as five minutes – and take somewhat longer to manifest after ingestion, typically approximately 15 minutes. With a very high dose, the onset of [[respiratory failure]] and [[brain death]] can occur in 15 to 30 minutes. If a lower dose is ingested, other symptoms begin to develop, including [[Epileptic seizure|seizures]], cramping, [[Muscle stiffness|stiffness]],<ref>{{cite journal | vauthors = Duverneuil C, de la Grandmaison GL, de Mazancourt P, Alvarez JC | title = Liquid chromatography/photodiode array detection for determination of strychnine in blood: a fatal case report | journal = Forensic Science International | volume = 141 | issue = 1 | pages = 17–21 | date = April 2004 | pmid = 15066709 | doi = 10.1016/j.forsciint.2003.12.010 | s2cid = 42860729}}</ref> [[hypervigilance]], and [[Agitation (dementia)|agitation]].<ref>{{cite journal | vauthors = Santhosh GJ, Joseph W, Thomas M | title = Strychnine poisoning | journal = The Journal of the Association of Physicians of India | volume = 51 | pages = 739–740 | date = July 2003 | pmid = 14621058}}</ref> Seizures caused by strychnine poisoning can start as early as 15 minutes after exposure and last 12–24 hours. They are often triggered by sights, sounds, or touch and can cause other adverse symptoms, including [[hyperthermia]], [[rhabdomyolysis]], myoglobinuric [[kidney failure]], [[metabolic acidosis]], and [[respiratory acidosis]]. During seizures, [[mydriasis]] (abnormal dilation), [[exophthalmos]] (protrusion of the eyes), and [[nystagmus]] (involuntary eye movements) may occur.<ref name="CDC_card" />

As strychnine poisoning progresses, [[tachycardia]] (rapid heart beat), [[hypertension]] (high blood pressure), [[tachypnea]] (rapid breathing), [[cyanosis]] (blue discoloration), [[diaphoresis]] (sweating), [[water-electrolyte imbalance]], [[leukocytosis]] (high number of [[white blood cell]]s), [[trismus]] (lockjaw), [[risus sardonicus]] (spasm of the facial muscles), and [[opisthotonus]] (dramatic spasm of the back muscles, causing arching of the back and neck) can occur. In rare cases, the affected person may experience [[nausea]] or [[vomiting]].<ref name="CDC_card" />

The proximate cause of death in strychnine poisoning can be [[cardiac arrest]], [[respiratory failure]], [[multiple organ failure]], or [[brain damage]].<ref name="CDC_card" />

{| class="wikitable sortable" style="margin-left:auto; margin-right:auto;"
|+ Minimum lethal dose estimates for strychnine in humans
|-
! scope="col" | Type
! scope="col" | Route
! scope="col" | Dose (mg)
! scope="col" class="unsortable" | Ref.
|-
| Human
| Oral
| 100–120
| <ref>{{cite book | date = January 15, 1994 | isbn = 978-0-8016-6676-6 | vauthors = Zenz C, Dickerson OB, Horvath EP | title = Occupational Medicine | edition = 3rd | page = 640 | location = St Louis | publisher = Mosby}}</ref><ref>{{cite journal | vauthors = Palatnick W, Meatherall R, Sitar D, Tenenbein M | title = Toxicokinetics of acute strychnine poisoning | journal = Journal of Toxicology. Clinical Toxicology | volume = 35 | issue = 6 | pages = 617–620 | pmid = 9365429 | doi = 10.3109/15563659709001242 | year = 1997 | s2cid = 26117078}}</ref>
|-
| Human
| Oral
| 30–60
| <ref>{{cite book | vauthors = Lewis RG | date = 1996 | title = Sax's Dangerous Properties of Industrial Materials | edition = 9th | volume = 1–3 | page = 3025 | publisher = Van Nostrand Reinhold | location = New York}}</ref>
|-
| Human (child)
| Oral
| 15
| <ref>{{cite book | vauthors = Goodman LS, Gilman AG, Gilman AM | title = The pharmalogical basis of therapeutics | date = 1985 | location = New York | publisher = Macmillan Publishing & Co., Inc}}</ref><ref name="gossel">{{cite book | vauthors = Gossel TA, Bricker JD | date = 1994 | title = Principles of Clinical Toxicology | edition = 3rd | page = [https://books.google.com/books?id=dAoFh3vGsFQC&pg=PA351 351] | publisher = Raven Press | location = New York}}</ref>
|-
| Human (adult)
| Oral
| 50–100
| <ref>{{cite journal | vauthors = Migliaccio E, Celentano R, Viglietti A, Viglietti G | title = Avvelenamento da stricnina. Un caso clinico | trans-title = Strychnine poisoning. A clinical case | journal = Minerva Anestesiologica | language = it | volume = 56 | issue = 1–2 | pages = 41–42 | year = 1990 | pmid = 2215981 | s2cid = 30164858}}</ref>
|-
| Human (adult)
| Oral
| 30–100
| <ref name="gossel" />
|-
| Human
| Intravenous
| 5–10 (approximate)
| <ref>{{cite book | veditors = Ellenhorn MJ, Schonwald S, Ordog G, Wasserberger J | chapter = Strychnine | title = Medical Toxicology: Diagnosis and Treatment of Human Poisoning. | location = Baltimore | publisher = Williams & Wilkins | date = 1997 | pages = 1660–1662}}</ref>
|}

For occupational exposures to strychnine, the [[Occupational Safety and Health Administration]] and the [[National Institute for Occupational Safety and Health]] have set exposure limits at 0.15&nbsp;mg/m<sup>3</sup> over an 8-hour work day.<ref name="PGCH">{{cite web | title = Strychnine | url = https://www.cdc.gov/niosh/npg/npgd0570.html | work = CDC – NIOSH Pocket Guide to Chemical Hazards | access-date = 2017-09-15 | archive-date = 2017-05-11 | archive-url = https://web.archive.org/web/20170511071949/https://www.cdc.gov/niosh/npg/npgd0570.html | url-status = live}}</ref>

Because strychnine produces some of the most dramatic and painful symptoms of any known toxic reaction, strychnine poisoning is often portrayed in literature and film including authors [[Agatha Christie]] and [[Arthur Conan Doyle]].<ref>{{cite web | title = Chemistry in its element – strychnine | url = http://www.rsc.org/chemistryworld/podcast/CIIEcompounds/transcripts/strychnine.asp | publisher = Royal Society of Chemistry | access-date = 18 May 2016 | archive-date = 23 June 2016 | archive-url = https://web.archive.org/web/20160623221712/http://www.rsc.org/chemistryworld/podcast/CIIEcompounds/transcripts/strychnine.asp | url-status = live}}</ref>

== Treatment ==
There is no [[antidote]] for strychnine poisoning.<ref>{{Cite web |date=2023-05-26 |title=Strychnine: Biotoxin {{!}} NIOSH {{!}} CDC |url=https://www.cdc.gov/niosh/ershdb/emergencyresponsecard_29750018.html |access-date=2024-08-12 |website=www.cdc.gov |language=en-us}}</ref> Strychnine poisoning demands aggressive management with early control of muscle spasms, intubation for loss of airway control, toxin removal ([[decontamination]]), intravenous hydration and potentially active cooling efforts in the context of hyperthermia as well as [[hemodialysis]] in kidney failure (strychnine has not been shown to be removed by hemodialysis).<ref name="CDC_card2">{{cite web |title=CDC – The Emergency Response Safety and Health Database: Biotoxin: Strychnine – NIOSH |url=https://www.cdc.gov/niosh/ershdb/emergencyresponsecard_29750018.html |url-status=live |archive-url=https://web.archive.org/web/20151221180423/http://www.cdc.gov/niosh/ershdb/emergencyresponsecard_29750018.html |archive-date=2015-12-21 |access-date=2016-01-02 |website=www.cdc.gov}}</ref> Treatment involves oral administration of [[activated charcoal]], which [[Adsorption|adsorbs]] strychnine within the digestive tract; unabsorbed strychnine is removed from the stomach by [[gastric lavage]], along with [[tannic acid]] or [[potassium permanganate]] solutions to oxidize strychnine.<ref>{{Cite journal |last=Patocka |first=Jiri |date=December 2015 |editor-last=Gupta |editor-first=Ramesh C. |title=Strychnine |url=https://www.researchgate.net/publication/282272675 |journal=Handbook of Toxicology of Chemical Warfare Agents |edition=2nd |publisher=Elsevier Inc. |pages=215–222 |doi=10.1016/B978-0-12-800159-2.00017-8 |isbn=978-0-12-800159-2 |via=ResearchGate}}</ref>

=== Activated charcoal ===
[[Activated carbon|Activated charcoal]] is a substance that can bind to certain toxins in the digestive tract and prevent their absorption into the bloodstream.<ref>{{cite web |title=Charcoal, Activated (Oral Route) Proper Use - Mayo Clinic |url=https://www.mayoclinic.org/drugs-supplements/charcoal-activated-oral-route/proper-use/drg-20070087 |url-status=live |archive-url=https://web.archive.org/web/20240206023304/https://www.mayoclinic.org/drugs-supplements/charcoal-activated-oral-route/proper-use/drg-20070087 |archive-date=2024-02-06 |access-date=2024-02-06 |website=[[Mayo Clinic]]}}</ref> The effectiveness of this treatment, as well as how long it is effective after ingestion, are subject to debate.<ref name="pmid150802072">{{cite journal |vauthors=Shadnia S, Moiensadat M, Abdollahi M |date=April 2004 |title=A case of acute strychnine poisoning |journal=Veterinary and Human Toxicology |volume=46 |issue=2 |pages=76–9 |pmid=15080207 |s2cid=23272093}}</ref><ref name="pmid290837952">{{cite book |title=Strychnine Toxicity |vauthors=Otter J, D'Orazio JL |date=August 7, 2023 |publisher=StatPearls |pmid=29083795 |id={{NCBIBook|NBK459306}}}}</ref><ref name="pmid85402352">{{cite journal |vauthors=Cooney DO |date=August 1995 |title=Evaluation of the US pharmacopeia adsorption tests for activated charcoals and proposals for changes |journal=Veterinary and Human Toxicology |volume=37 |issue=4 |pages=371–7 |pmid=8540235 |s2cid=67975596}}</ref> According to one source, activated charcoal is only effective within one hour of poison being ingested, although the source does not regard strychnine specifically.<ref>{{cite journal |last=Lapus |first=Robert Michael |date=April 2007 |title=Activated charcoal for pediatric poisonings: the universal antidote? |url=https://emergency.med.ufl.edu/files/2013/02/Activated-charcoal.pdf |url-status=live |journal=Current Opinion in Pediatrics |volume=19 |issue=2 |pages=216–222 |doi=10.1097/MOP.0b013e32801da2a9 |pmid=17496769 |s2cid=6728477 |archive-url=https://web.archive.org/web/20240206022505/https://emergency.med.ufl.edu/files/2013/02/Activated-charcoal.pdf |archive-date=2024-02-06 |access-date=2024-02-06}}</ref> Other sources specific to strychnine state that activated charcoal may be used after one hour of ingestion, depending on dose and type of strychnine-containing product.<ref>{{cite journal |vauthors=Hayden JW, Comstock EG |date=1975 |title=Use of Activated Charcoal in Acute Poisoning |url=https://www.tandfonline.com/doi/pdf/10.3109/15563657508988096 |url-status=live |journal=Clinical Toxicology |volume=8 |issue=5 |pages=515–533 |doi=10.3109/15563657508988096 |pmid=770060 |s2cid=42542989 |archive-url=https://web.archive.org/web/20240308030358/https://www.tandfonline.com/doi/pdf/10.3109/15563657508988096 |archive-date=2024-03-08 |access-date=2024-02-06|url-access=subscription }}</ref><ref name="pmid290837952" /> Therefore, other treatment options are generally favoured over activated charcoal.<ref name="pmid290837952" /><ref>{{cite web |date=16 January 2020 |title=CDC Strychnine &#124; Facts about Strychnine &#124; Public Health Emergency Preparedness& Response |url=https://emergency.cdc.gov/agent/strychnine/basics/facts.asp |url-status=live |archive-url=https://web.archive.org/web/20240206022505/https://emergency.cdc.gov/agent/strychnine/basics/facts.asp |archive-date=6 February 2024 |access-date=6 February 2024}}</ref> 

The use of activated charcoal is considered dangerous in patients with tenuous airways or altered mental states.<ref>{{cite journal |vauthors=Smith BA |year=1990 |title=Strychnine poisoning |journal=The Journal of Emergency Medicine |volume=8 |issue=3 |pages=321–325 |doi=10.1016/0736-4679(90)90013-L |pmid=2197324}}</ref> 

=== Other treatments ===
Most other treatment options focus on controlling the convulsions that arise from strychnine poisoning. These treatments involve keeping the patient in a quiet and darkened room,<ref>{{Cite web |title=Drugs and Poisons Fact Sheet: Strychnine Permits - What you need to know |url=https://www.bulloo.qld.gov.au/downloads/file/978/9-strychnine-guide |access-date=12 August 2024 |publisher=Queensland Health}}</ref> [[anticonvulsants]] such as [[phenobarbital]] or [[diazepam]],<ref name="CDC_card2" /> muscle relaxants such as [[dantrolene]],<ref>{{Cite web |title=Final Diagnosis -- Case 550 |url=https://path.upmc.edu/cases/case550/dx.html |access-date=2024-08-12 |website=path.upmc.edu}}</ref> barbiturates and [[propofol]],<ref>{{cite journal |vauthors=Lages A, Pinho J, Alves R, Capela C, Lourenço E, Lencastre L |date=16 May 2013 |title=Strychnine Intoxication: A Case Report |journal=Journal of Medical Cases |volume=4 |issue=6 |pages=385–388 |doi=10.4021/jmc1189w |s2cid=54707248 |doi-access=free}}</ref> and [[chloroform]] or heavy doses of [[chloral]], [[bromide]], [[Ethyl carbamate|urethane]] or [[amyl nitrite]].<ref>{{cite book |title=Pharmacology and Therapeutics |vauthors=Cushny AR |date=January 1, 1940 |publisher=Lea & Febiger |edition=12 |asin=B000SNDA1U}}</ref><ref name="pmid296408802">{{cite journal |vauthors=Buckley S |date=September 1873 |title=Case of Strychnine Poisoning Successfully Treated by Atropine |journal=Edinburgh Medical Journal |volume=19 |issue=3 |pages=211–213 |pmc=5315983 |pmid=29640880 |s2cid=4760315}}</ref><ref>{{cite journal |date=1932 |title=The Treatment of Strychnine Poisoning |url=https://jamanetwork.com/journals/jama/article-abstract/280615 |url-status=live |journal=Journal of the American Medical Association |volume=98 |issue=23 |page=1992 |doi=10.1001/jama.1932.02730490038013 |archive-url=https://web.archive.org/web/20240206023304/https://jamanetwork.com/journals/jama/article-abstract/280615 |archive-date=2024-02-06 |access-date=2024-02-06|url-access=subscription }}</ref><ref>{{cite web |date=8 September 2021 |title=Strychnine and Vomit: The Untold Story of Past US Addiction Treatments |url=https://filtermag.org/strychnine-addiction-treatments/ |url-status=live |archive-url=https://web.archive.org/web/20240206023305/https://filtermag.org/strychnine-addiction-treatments/ |archive-date=6 February 2024 |access-date=6 February 2024}}</ref> If a poisoned person is able to survive for 6 to 12 hours subsequent to initial dose, they have a good prognosis.<ref name="CDC_card2" />

The [[Sine qua non#Usage in medicine|sine qua non]] of strychnine toxicity is the "awake" seizure, in which tonic-clonic activity occurs but the patient is alert and oriented throughout and afterwards.<ref>{{cite journal |vauthors=Boyd RE, Brennan PT, Deng JF, Rochester DF, Spyker DA |date=March 1983 |title=Strychnine poisoning. Recovery from profound lactic acidosis, hyperthermia, and rhabdomyolysis |journal=The American Journal of Medicine |volume=74 |issue=3 |pages=507–512 |doi=10.1016/0002-9343(83)90999-3 |pmid=6829597 |s2cid=3222667}}</ref> Accordingly, [[George Harley (physician)|George Harley]] (1829–1896) showed in 1850 that [[curare]] (wourali) was [[Curare#History|effective]] for the treatment of tetanus and strychnine poisoning.

== Usage as a drug ==
Strychnine was commonly used as an athletic [[Performance-enhancing substance|performance enhancer]] and [[stimulant]] in the late 19th century and early 20th century.<ref>{{cite book |last=Donohoe |first=Tom |last2=Johnson |first2=Neil |title=Foul Play: Drug Abuse in Sports |publisher=Basil Blackwell |location=Oxford, England |date=1986 |isbn=978-0-631-14844-9}}<br /><br />It is known that many of these riders were given strychnine during competition.<br /><br />At very low doses, strychnine has a stimulant effect, but at higher doses is extremely poisonous. (1. Introduction, pages 3 & 4)<br /><br />Also see pages 5 and 7.</ref> The most well known incident of this usage was during the [[1904 Summer Olympics|1904 Olympics]] marathon, when track-and-field athlete [[Thomas Hicks (athlete)|Thomas Hicks]] was administered a concoction of egg whites and brandy that contained strychnine by his assistants in an attempt to boost his stamina; Hicks did not know that it contained strychnine.<ref>{{cite book |last=Goldman |first=Bob |last2=Klatz |first2=Ronald |last3=Bush |first3=Patricia J. |title=Death in the Locker Room: Steroids and Sports |publisher=The Body Press |location=Tucson, AZ |date=1984 |isbn=978-0-89586-597-7}}<br />In 1904, the games were in St. Louis, and it took four frantic physicians to revive Tom Hicks, who collapsed after he won the marathon. The physicians discovered that Hicks had taken a large dose of strychnine and brandy before he went out on the track. (Drugs in Sports Means the Death of Sports, p. 27)</ref><ref>{{cite magazine | last1 = Abbott | first1 = Karen | author-link1 = Karen Abbott | date = August 7, 2012 | title = The 1904 Olympic Marathon May Have Been the Strangest Ever | magazine = Smithsonian Magazine | language = en | url = https://www.smithsonianmag.com/history/the-1904-olympic-marathon-may-have-been-the-strangest-ever-14910747/ | access-date = April 8, 2024 | quote = He began hallucinating, believing that the finish line was still 20 miles away.}}</ref><ref>{{cite web | title = Thomas Hicks | url = https://www.olympedia.org/athletes/78551 | access-date = January 17, 2021 | work = Olympedia}}</ref>

[[Maximilian Theodor Buch]] proposed that strychnine was a cure for alcoholism.<ref>{{cite news |title=News Briefs |url=https://www.newspapers.com/image/436941471/?match=1&terms=Strychnine%20abuse |access-date=4 June 2024 |publisher=[[The Sioux City Journal]] |date=14 November 1908}}</ref>

{{clarify span|{{quote|… "After a time I crawled home, took some food and a strong dose of strychnine, and went to sleep in my clothes on my unmade bed. Strychnine is a grand tonic, Kemp, to take the flabbiness out of a man." 

"It's the devil," said Kemp. "It's the palaeolithic in a bottle." 

"I awoke vastly invigorated and rather irritable. You know?" 

"I know the stuff."|author=H. G. Wells<ref>{{cite book |last=Wells |first=H. G. |title=The Invisible Man |date=1897 |chapter=Chapter 20: At the House in Great Portland Street |publisher=C. Arthur Pearson}}</ref>}}|reason=This quotation needs context clarifying its relevance to the article|date=September 2025}} The Invisible Man (1897) Griffin, the protagonist, is a strychnine addict.

== Pharmacokinetics ==

=== Absorption ===
Strychnine may be introduced into the body orally, by inhalation, or by injection. It is a potently bitter substance, and in humans has been shown to activate [[Taste receptor#Bitter|bitter taste receptors]] [[TAS2R10]] and [[TAS2R46]].<ref name="Meyerhof2010">{{cite journal | vauthors = Meyerhof W, Batram C, Kuhn C, Brockhoff A, Chudoba E, Bufe B, Appendino G, Behrens M | title = The molecular receptive ranges of human TAS2R bitter taste receptors | journal = Chemical Senses | volume = 35 | issue = 2 | pages = 157–170 | date = February 2010 | pmid = 20022913 | doi = 10.1093/chemse/bjp092 | doi-access = free | s2cid = 15537937}}</ref><ref name="Born2013">{{cite journal | vauthors = Born S, Levit A, Niv MY, Meyerhof W, Behrens M | title = The human bitter taste receptor TAS2R10 is tailored to accommodate numerous diverse ligands | journal = The Journal of Neuroscience | volume = 33 | issue = 1 | pages = 201–213 | date = January 2013 | pmid = 23283334 | pmc = 6618634 | doi = 10.1523/JNEUROSCI.3248-12.2013 | s2cid = 17263291}}</ref><ref name="Meyerhof2011">{{cite journal | vauthors = Meyerhof W, Born S, Brockhoff A, Behrens M | doi = 10.1002/ffj.2041 | title = Molecular biology of mammalian bitter taste receptors. A review | journal = Flavour and Fragrance Journal | volume = 26 | issue = 4 | pages = 260–268 | year = 2011 | s2cid = 82519304}}</ref> Strychnine is rapidly absorbed from the gastrointestinal tract.<ref>{{cite journal | vauthors = Lambert JR, Byrick RJ, Hammeke MD | title = Management of acute strychnine poisoning | journal = Canadian Medical Association Journal | volume = 124 | issue = 10 | pages = 1268–1270 | date = May 1981 | pmid = 7237316 | pmc = 1705440}}</ref>

=== Distribution ===
Strychnine is transported by [[Blood plasma|plasma]] and [[red blood cell]]s. Due to slight [[Plasma protein binding|protein binding]], strychnine leaves the bloodstream quickly and distributes to bodily tissues. Approximately 50% of the ingested dose can enter the tissues in 5 minutes. Also within a few minutes of ingestion, strychnine can be detected in the urine. Little difference was noted between oral and intramuscular administration of strychnine in a 4&nbsp;mg dose.<ref>{{cite book | title = Handbook of toxicology of chemical warfare agents | vauthors = Gupta RC | year = 2009 | publisher = Elsevier/Academic Press | isbn = 978-0-12-800159-2 | oclc = 433545336}}</ref> In persons killed by strychnine, the highest concentrations are found in the blood, liver, kidney and stomach wall. The usual fatal dose is 60–100&nbsp;mg strychnine and is fatal after a period of 1–2 hours, though lethal doses vary depending on the individual.

=== Metabolism ===
Strychnine is rapidly metabolized by the liver microsomal enzyme system requiring [[NADPH]] and O<sub>2</sub>. Strychnine competes with the inhibitory [[neurotransmitter]] [[glycine]] resulting in an excitatory state. However, the [[toxicokinetics]] after overdose have not been well described. In most severe cases of strychnine poisoning, the patient dies before reaching the hospital. The [[biological half-life]] of strychnine is about 10 hours.

=== Excretion ===
A few minutes after ingestion, strychnine is excreted unchanged in the urine, and accounts for about 5 to 15% of a sublethal dose given over 6 hours. Approximately 10 to 20% of the dose will be excreted unchanged in the urine in the first 24 hours. The percentage excreted decreases with the increasing dose. Of the amount excreted by the kidneys, about 70% is excreted in the first 6 hours, and almost 90% in the first 24 hours. Excretion is virtually complete in 48 to 72 hours.<ref name="gupta" />

== History ==
Strychnine was the first alkaloid to be identified in plants of the genus ''[[Strychnos]]'', family [[Loganiaceae]]. ''Strychnos'', named by [[Carl Linnaeus]] in 1753, is a [[genus]] of trees and climbing [[shrub]]s of the [[Gentianales]] order. The genus contains 196 various species and is distributed throughout the warm regions of Asia (58 species), America (64 species), and Africa (75 species). The seeds and bark of many plants in this genus contain strychnine.

The toxic and medicinal effects of ''[[Strychnos nux-vomica]]'' have been well known from the times of ancient India, although the chemical compound itself was not identified and characterized until the 19th century. The inhabitants of these countries had historical knowledge of the species ''Strychnos nux-vomica'' and Saint-Ignatius' bean (''[[Strychnos ignatii]]''). ''Strychnos nux-vomica'' is a tree native to the [[tropical forest]]s on the [[Malabar Coast]] in Southern India, Sri Lanka and Indonesia, which attains a height of about {{convert|12|m}}. The tree has a crooked, short, thick trunk and the wood is close grained and very durable. The fruit has an orange color and is about the size of a large apple with a hard [[Peel (fruit)|rind]] and contains five seeds, which are covered with a soft wool-like substance. The ripe seeds look like flattened disks, which are very hard. These seeds are the chief commercial source of strychnine and were first imported to and marketed in Europe as a poison to kill rodents and small [[predator]]s. ''Strychnos ignatii'' is a woody climbing shrub of the Philippines. The fruit of the plant, known as Saint Ignatius' bean, contains as many as 25 seeds embedded in the pulp. The seeds contain more strychnine than other commercial alkaloids. The properties of ''S. nux-vomica'' and ''S. ignatii'' are substantially those of the alkaloid strychnine.

Strychnine was first discovered by French chemists [[Joseph Bienaimé Caventou]] and [[Pierre-Joseph Pelletier]] in 1818 in the Saint-Ignatius' bean.<ref>{{cite journal | vauthors = Pelletier PP, Caventou JB | author-link1 = Pierre-Joseph Pelletier | author-link2 = Joseph Bienaimé Caventou | year = 1818 | title = Note sur un nouvel alkalai | trans-title = Note on a new alkali | language = fr | url = https://books.google.com/books?id=-N43AAAAMAAJ&pg=PA323 | journal = Annales de Chimie et de Physique | volume = 8 | pages = 323–324 | access-date = 2016-10-06 | archive-date = 2024-03-08 | archive-url = https://web.archive.org/web/20240308030358/https://books.google.com/books?id=-N43AAAAMAAJ&pg=PA323#v=onepage&q&f=false | url-status = live}}</ref><ref>{{cite journal | vauthors = Pelletier PP, Caventou JB | date = 1819 | url = https://books.google.com/books?id=sSE4AQAAIAAJ&pg=PA142 | title = Mémoire sur un nouvel alcali vegetal (la strychnine) trouvé dans la feve de Saint-Ignace, la noix vomique, etc. | trans-title = Memoir on a new vegetable alkali (strychnine) found in the St. Ignatius bean, the nux-vomica, etc) | language = fr | journal = Annales de Chimie et de Physique | volume = 10 | pages = 142–176 | access-date = 2016-10-06 | archive-date = 2024-03-08 | archive-url = https://web.archive.org/web/20240308030358/https://books.google.com/books?id=sSE4AQAAIAAJ&pg=PA142#v=onepage&q&f=false | url-status = live}}</ref> In some ''Strychnos'' plants a 9,10-dimethoxy derivative of strychnine, the alkaloid [[brucine]], is also present. [[Brucine]] is not as poisonous as strychnine. Historic records indicate that preparations containing strychnine (presumably) had been used to kill dogs, cats, and birds in Europe as far back as 1640.<ref name="gupta">{{cite book | vauthors = Gupta RC, Patocka J | date = 2009 | title = Handbook of Toxicology of Chemical Warfare Agents | url = https://books.google.com/books?id=OVpNT6Vpkx8C&q=1640 | location = London | publisher = Academic Press | page = 199 | isbn = 978-0-08-092273-7 | access-date = 2020-10-20 | archive-date = 2024-03-08 | archive-url = https://web.archive.org/web/20240308030358/https://books.google.com/books?id=OVpNT6Vpkx8C&q=1640#v=snippet&q=1640&f=false | url-status = live}}</ref> It was allegedly used by convicted murderer [[William Palmer (murderer)|William Palmer]] to kill his final victim, John Cook.<ref name="rugeley poisoner">{{cite book | last = Hayhurst | first = Alan | title = Staffordshire MURDERS | year = 2008 | publisher = The History Press | location = [[Gloucestershire]] | isbn = 978-0-7509-4706-0 | pages = 15–36}}</ref> It was also used during [[World War II]] by [[Oskar Dirlewanger]] against civilians.<ref>{{cite book | vauthors = Grunberger R | title = The 12-Year Reich: A Social History of Nazi Germany, 1933–1945 | publisher = Holt, Rinehart and Winston | date = 1971 | page = 104}}</ref>

The structure of strychnine was first determined in 1946 by Sir [[Robert Robinson (organic chemist)|Robert Robinson]] and in 1954 this alkaloid was [[Strychnine total synthesis|synthesized]] in a laboratory by [[Robert Burns Woodward|Robert B. Woodward]]. This is one of the most famous syntheses in the history of organic chemistry. Both chemists won the [[Nobel Prize in Chemistry|Nobel prize]] (Robinson in 1947 and Woodward in 1965).<ref name="gupta" />

Strychnine has been used as a plot device in the author [[Agatha Christie]]'s murder mysteries.<ref name="strichnine1">{{cite web | title = Killed by Agatha Christie: Strychnine and the detective novel | url = http://www.open.edu/openlearn/history-the-arts/culture/literature-and-creative-writing/literature/killed-agatha-christie-strychnine-and-the-detective-novel | website = www.open.edu | publisher = [[Open University]] | access-date = 27 July 2017 | archive-date = 20 August 2017 | archive-url = https://web.archive.org/web/20170820221016/http://www.open.edu/openlearn/history-the-arts/culture/literature-and-creative-writing/literature/killed-agatha-christie-strychnine-and-the-detective-novel | url-status = live}}</ref>

== See also ==
* [[Avicide]]

== References ==
{{Reflist}}

{{Chemical agents}}
{{Rodenticides}}
{{Glycinergics}}
{{Convulsants}}
{{Neurotoxins}}

{{Authority control}}

[[Category:Avicides]]
[[Category:Bitter compounds]]
[[Category:Chloride channel blockers]]
[[Category:Convulsants]]
[[Category:Ethers]]
[[Category:Glycine receptor antagonists]]
[[Category:Indole alkaloids]]
[[Category:Lactams]]
[[Category:Neurotoxins]]
[[Category:Nitrogen heterocycles]]
[[Category:Oxygen heterocycles]]
[[Category:Plant toxins]]
[[Category:Strychnine poisoning]]