Editing Atropine

{{Short description|Anticholinergic medication used as antidote for nerve agent poisoning}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Drugbox
| Verifiedfields     = changed
| Watchedfields      = changed
| verifiedrevid      = 458781584
| caption            = 
| image              = Atropine-D-and-L-isomers-from-DL-xtal-2004-3D-balls.png
| width              = 300
| alt                = 

<!--Clinical data-->
| tradename          = Atropen, others
| synonyms           = Daturin<ref>{{cite book|url=https://archive.org/details/mobot31753000788254 |page=[https://archive.org/details/mobot31753000788254/page/148 148] |title=Medical Flora; Or, Manual of the Medical Botany of the United States of ... - Constantine Samuel Rafinesque - Internet Archive |publisher=Atkinson & Alexander |access-date=2012-11-07|year=1828| vauthors = Rafinesque CS }}</ref>
| Drugs.com          = {{drugs.com|monograph|atropine}}
| MedlinePlus        = a682487
| licence_EU         = 
| licence_US         = 
| DailyMedID         = Atropine
| pregnancy_AU       = A
| routes_of_administration = [[Oral administration|By mouth]], [[Intravenous therapy|intravenous]], [[Intramuscular injection|intramuscular]], [[Rectal administration|rectal]], [[Ophthalmic drug administration|ophthalmic]]
| class              = [[antimuscarinic]] (anticholinergic)
| ATC_prefix         = A03
| ATC_suffix         = BA01
| ATC_supplemental   = {{ATC|S01|FA01}}

<!-- Legal status -->| pregnancy_category = 
| legal_AU           = S4
| legal_AU_comment   =<ref>{{cite web | title=AusPAR: Atropine sulfate monohydrate | website=Therapeutic Goods Administration (TGA) | date=31 May 2022 | url=https://www.tga.gov.au/auspar/auspar-atropine-sulfate-monohydrate | access-date=12 June 2022 | archive-date=31 May 2022 | archive-url=https://web.archive.org/web/20220531202918/http://www.tga.gov.au/auspar/auspar-atropine-sulfate-monohydrate | url-status=live }}</ref>
| legal_BR           = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment   = 
| legal_CA           = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment   = 
| legal_DE           = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment   = 
| legal_NZ           = <!-- Class A, B, C -->
| legal_NZ_comment   = 
| legal_UK           = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment   = 
| legal_US           = Rx-only
| legal_US_comment   =<ref name="Atropine sulfate FDA label" /><ref>{{cite web | title=Atropine- atropine sulfate solution/ drops | website=DailyMed | date=22 February 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=127a7e32-a150-01d6-a66a-b7708d85809f | access-date=16 March 2022 | archive-date=16 March 2022 | archive-url=https://web.archive.org/web/20220316210929/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=127a7e32-a150-01d6-a66a-b7708d85809f | url-status=live }}</ref>
| legal_EU           = 
| legal_EU_comment   = 
| legal_UN           = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment   = 
| legal_status       = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->| bioavailability    = 25%
| metabolism         = ≥50% [[hydrolyse]]d to [[tropine]] and [[tropic acid]]
| onset              = c. 1 minute<ref name=Bar2009/>
| elimination_half-life = 2 hours
| duration_of_action = 30 to 60 min<ref name=Bar2009/>
| excretion          = 15–50% excreted unchanged in urine

<!--Identifiers-->| CAS_number_Ref     = {{cascite|correct|??}}
| CAS_number         = 51-55-8
| PubChem            = 174174
| IUPHAR_ligand      = 320
| DrugBank_Ref       = {{drugbankcite|correct|drugbank}}
| DrugBank           = DB00572
| ChemSpiderID_Ref   = {{chemspidercite|correct|chemspider}}
| ChemSpiderID       = 10194105
| UNII_Ref           = {{fdacite|correct|FDA}}
| UNII               = 7C0697DR9I
| KEGG_Ref           = {{keggcite|correct|kegg}}
| KEGG               = D00113
| ChEBI_Ref          = {{ebicite|correct|EBI}}
| ChEBI              = 16684
| ChEMBL_Ref         = 
| ChEMBL             = 517712

<!--Chemical data-->| drug_name          = 
| type               = 
| IUPAC_name         = (''RS'')-(8-Methyl-8-azabicyclo[3.2.1]oct-3-yl) 3-hydroxy-2-phenylpropanoate
| C                  = 17
| H                  = 23
| N                  = 1
| O                  = 3
| smiles             = CN3[C@H]1CC[C@@H]3C[C@@H](C1)OC(=O)C(CO)c2ccccc2
| StdInChI_Ref       = {{stdinchicite|correct|chemspider}}
| StdInChI           = 1S/C17H23NO3/c1-18-13-7-8-14(18)10-15(9-13)21-17(20)16(11-19)12-5-3-2-4-6-12/h2-6,13-16,19H,7-11H2,1H3/t13-,14+,15+,16?
| StdInChIKey_Ref    = {{stdinchicite|correct|chemspider}}
| StdInChIKey        = RKUNBYITZUJHSG-SPUOUPEWSA-N
}}
<!-- Definition and medical uses -->
'''Atropine''' is a [[tropane alkaloid]] and [[anticholinergic]] medication used to treat certain types of [[nerve agent]] and [[pesticide poisoning]]s as well as some types of [[bradycardia|slow heart rate]], and to decrease [[saliva]] production during surgery.<ref name=AHFS2015>{{cite web|title=Atropine|url=https://www.drugs.com/monograph/atropine.html|publisher=The American Society of Health-System Pharmacists|access-date=Aug 13, 2015|url-status=live|archive-url=https://web.archive.org/web/20150712191611/http://www.drugs.com/monograph/atropine.html|archive-date=2015-07-12}}</ref> It is typically given [[intravenously]] or by injection [[intramuscular|into a muscle]].<ref name=AHFS2015/> [[Ophthalmic drug administration|Eye drops]] are also available which are used to treat [[uveitis]] and early [[amblyopia]].<ref name=Ric2014>{{cite book| vauthors = Hamilton RJ, Duffy AN, Stone D, Spencer A |title=Tarascon pharmacopoeia|date=2014|isbn=9781284056716|page=386|publisher=Jones & Bartlett Publishers |edition=15|url=https://books.google.com/books?id=F6YdAwAAQBAJ&pg=PA386|url-status=live|archive-url=https://web.archive.org/web/20151002131018/https://books.google.ca/books?id=F6YdAwAAQBAJ&pg=PA386|archive-date=2015-10-02}}</ref><ref name="National Eye Institute 2019">{{cite web | title=Amblyopia (Lazy Eye) | website=National Eye Institute | date=2019-07-02 | url=https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/amblyopia-lazy-eye | access-date=2020-01-31 | quote=Putting special eye drops in the stronger eye. A once-a-day drop of the drug atropine can temporarily blur near vision, which forces the brain to use the other eye. For some children, this treatment works as well as an eye patch, and some parents find it easier to use (for example, because young children may try to pull off eye patches). | archive-date=2020-01-31 | archive-url=https://web.archive.org/web/20200131061230/https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/amblyopia-lazy-eye | url-status=live }}</ref> The intravenous solution usually begins working within a minute and lasts half an hour to an hour.<ref name=Bar2009>{{cite book| vauthors = Barash PG |title=Clinical anesthesia|date=2009|publisher=Wolters Kluwer/Lippincott Williams & Wilkins|location=Philadelphia|isbn=9780781787635|page=525|edition=6th|url=https://books.google.com/books?id=-YI9P2DLe9UC&pg=PA525|url-status=live|archive-url=https://web.archive.org/web/20151124084028/https://books.google.ca/books?id=-YI9P2DLe9UC&pg=PA525|archive-date=2015-11-24}}</ref> Large doses may be required to treat some poisonings.<ref name=AHFS2015/>

<!-- Side effects and mechanism -->
Common [[side effects]] include [[Xerostomia|dry mouth]], [[mydriasis|abnormally large pupils]], [[urinary retention]], [[constipation]], and a [[tachycardia|fast heart rate]].<ref name=AHFS2015/> It should generally not be used in people with [[angle closure glaucoma|closed-angle glaucoma]].<ref name=AHFS2015/> While there is no evidence that its use during pregnancy causes [[birth defects]], this has not been well studied so sound clinical judgment should be used.<ref name=Breast2015/> It is likely safe during breastfeeding.<ref name=Breast2015>{{cite web|title=Atropine Pregnancy and Breastfeeding Warnings|url=https://www.drugs.com/pregnancy/atropine.html|access-date=14 August 2015|url-status=live|archive-url=https://web.archive.org/web/20150906151324/http://www.drugs.com/pregnancy/atropine.html|archive-date=6 September 2015}}</ref> It is an [[antimuscarinic]] (a type of anticholinergic) that works by inhibiting the [[parasympathetic nervous system]].<ref name=AHFS2015/>

<!-- History, society and culture -->
Atropine occurs naturally in a number of plants of the [[Solanaceae|nightshade family]], including [[Atropa belladonna|deadly nightshade]] (''Atropa belladonna''), [[Datura stramonium|jimsonweed]] (''Datura stramonium''), [[Mandragora officinarum|mandrake]] (''Mandragora officinarum'')<ref>{{cite book| vauthors = Brust JC |title=Neurological aspects of substance abuse|date=2004|publisher=Elsevier|location=Philadelphia|isbn=9780750673136|page=310|edition=2|url=https://books.google.com/books?id=fOfxoQm_a7MC&pg=PA310|url-status=live|archive-url=https://web.archive.org/web/20151002123816/https://books.google.ca/books?id=fOfxoQm_a7MC&pg=PA310|archive-date=2015-10-02}}</ref> and [[Brugmansia|angel's trumpet]] (''Brugmansia'').<ref>{{cite journal | vauthors = Kim Y, Kim J, Kim OJ, Kim WC | title = Intoxication by angel's trumpet: case report and literature review | journal = BMC Research Notes | volume = 7 | pages = 553 | date = August 2014 | pmid = 25138632 | pmc = 4148940 | doi = 10.1186/1756-0500-7-553 | doi-access = free }}</ref> Atropine was first isolated in 1833.<ref>{{cite book| vauthors = Ainsworth S |title=Neonatal Formulary: Drug Use in Pregnancy and the First Year of Life|date=2014|publisher=John Wiley & Sons|isbn=9781118819593|page=94|url=https://books.google.com/books?id=VOLhBQAAQBAJ&pg=PA94|url-status=live|archive-url=https://web.archive.org/web/20151002140026/https://books.google.ca/books?id=VOLhBQAAQBAJ&pg=PA94|archive-date=2015-10-02}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref> It is available as a [[generic medication]].<ref name=AHFS2015/><ref>{{cite book| vauthors = Hamilton RJ |title=Tarascon pharmacopoeia|date=2014|isbn=9781284056716|page=386|publisher=Jones & Bartlett Publishers |edition=15|url=https://books.google.com/books?id=F6YdAwAAQBAJ&pg=PA386|url-status=live|archive-url=https://web.archive.org/web/20151002131018/https://books.google.ca/books?id=F6YdAwAAQBAJ&pg=PA386|archive-date=2015-10-02}}</ref><ref>{{cite web | title=Competitive Generic Therapy Approvals | website=U.S. [[Food and Drug Administration]] (FDA) | date=29 June 2023 | url=https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals | access-date=29 June 2023 | archive-date=29 June 2023 | archive-url=https://web.archive.org/web/20230629233651/https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals | url-status=dead }}</ref>

== Medical uses ==
[[File:Atropine injection ampoule.JPG|thumb|An [[ampoule]] containing atropine injection 0.5mg/1mL]]

=== Eyes ===
[[Ophthalmic drug administration|Topical]] atropine is used as a [[cycloplegic]], to temporarily paralyze the [[accommodation reflex]], and as a [[mydriatic]], to dilate the [[pupil]]s.<ref name="pmid29132914"/> Atropine degrades slowly, typically wearing off in 7 to 14 days, so it is generally used as a therapeutic [[mydriatic]], whereas [[tropicamide]] (a shorter-acting [[cholinergic]] antagonist) or [[phenylephrine]] (an α-adrenergic agonist) is preferred as an aid to [[Ophthalmology|ophthalmic]] examination.<ref name="pmid29132914">{{cite journal | vauthors = Yazdani N, Sadeghi R, Momeni-Moghaddam H, Zarifmahmoudi L, Ehsaei A | title = Comparison of cyclopentolate versus tropicamide cycloplegia: A systematic review and meta-analysis | journal = Journal of Optometry | volume = 11 | issue = 3 | pages = 135–143 | date = 2018 | pmid = 29132914 | pmc = 6039578 | doi = 10.1016/j.optom.2017.09.001 }}</ref>

In refractive and accommodative [[amblyopia]], when occlusion is not appropriate sometimes atropine is given to induce blur in the good eye.<ref>{{cite journal | vauthors = Georgievski Z, Koklanis K, Leone J | year = 2008 | title = Fixation behavior in the treatment of amblyopia using atropine | journal = Clinical and Experimental Ophthalmology | volume = 36 | issue = Suppl 2| pages = A764–A765 }}</ref> Evidence suggests that atropine penalization is just as effective as occlusion in improving visual acuity.<ref>{{Cite journal |date=2019-12-05 |title=A patch or eye drops are similarly effective for the treatment of "lazy eye" in children |url=https://evidence.nihr.ac.uk/alert/a-patch-or-eye-drops-are-similarly-effective-for-the-treatment-of-lazy-eye-in-children |journal=NIHR Evidence |type=Plain English summary |publisher=National Institute for Health and Care Research |doi=10.3310/signal-000849 |s2cid=243130859 |access-date=2022-09-16 |archive-date=2024-05-26 |archive-url=https://web.archive.org/web/20240526050121/https://evidence.nihr.ac.uk/alert/a-patch-or-eye-drops-are-similarly-effective-for-the-treatment-of-lazy-eye-in-children/ |url-status=live |url-access=subscription }}</ref><ref>{{cite journal | vauthors = Li T, Qureshi R, Taylor K | title = Conventional occlusion versus pharmacologic penalization for amblyopia | journal = The Cochrane Database of Systematic Reviews | volume = 8 | pages = CD006460 | date = August 2019 | issue = 8 | pmid = 31461545 | pmc = 6713317 | doi = 10.1002/14651858.CD006460.pub3 }}</ref>

Antimuscarinic topical medication is effective in slowing myopia progression in children; accommodation difficulties and papillae and follicles are possible side effects.<ref>{{Cite journal|vauthors=Walline JJ, Lindsley KB, Vedula SS, Cotter SA, Mutti DO, Ng SM, Twelker JD|date=13 Jan 2020|title=Interventions to slow progression of myopia in children|journal=Cochrane Database Syst Rev|volume=1|issue=9|pages=CD004916|doi=10.1002/14651858.CD004916.pub4|pmid=31930781|pmc=6984636}}</ref> All doses of atropine appear similarly effective, while higher doses have greater side effects.<ref name="Gong2017">{{cite journal | vauthors = Gong Q, Janowski M, Luo M, Wei H, Chen B, Yang G, Liu L | title = Efficacy and Adverse Effects of Atropine in Childhood Myopia: A Meta-analysis | journal = JAMA Ophthalmology | volume = 135 | issue = 6 | pages = 624–630 | date = June 2017 | pmid = 28494063 | pmc = 5710262 | doi = 10.1001/jamaophthalmol.2017.1091 }}</ref> The lower dose of 0.01% is thus generally recommended due to fewer side effects and potential less rebound worsening when the atropine is stopped.<ref name="Gong2017" /><ref>{{cite journal | vauthors = Fricke T, Hurairah H, Huang Y, Ho SM | title = Pharmacological interventions in myopia management | journal = Community Eye Health | volume = 32 | issue = 105 | pages = 21–22 | date = 2019 | pmid = 31409953 | pmc = 6688412 }}</ref>

=== Heart ===
[[Injection (medicine)|Injection]]s of atropine are used in the treatment of symptomatic or unstable [[bradycardia]].

Atropine was previously included in international resuscitation guidelines for use in cardiac arrest associated with [[asystole]] and [[pulseless electrical activity|PEA]] but was removed from these guidelines in 2010 due to a lack of evidence for its effectiveness.<ref>{{cite journal | vauthors = Field JM, Hazinski MF, Sayre MR, Chameides L, Schexnayder SM, Hemphill R, Samson RA, Kattwinkel J, Berg RA, Bhanji F, Cave DM, Jauch EC, Kudenchuk PJ, Neumar RW, Peberdy MA, Perlman JM, Sinz E, Travers AH, Berg MD, Billi JE, Eigel B, Hickey RW, Kleinman ME, Link MS, Morrison LJ, O'Connor RE, Shuster M, Callaway CW, Cucchiara B, Ferguson JD, Rea TD, Vanden Hoek TL | title = Part 1: executive summary: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care | journal = Circulation | volume = 122 | issue = 18 Suppl 3 | pages = S640-56 | date = November 2010 | pmid = 20956217 | doi = 10.1161/CIRCULATIONAHA.110.970889 | s2cid = 1031566 | doi-access =  }}</ref>  For symptomatic bradycardia, the usual dosage is 0.5 to 1&nbsp;mg IV push; this may be repeated every 3 to 5 minutes, up to a total dose of 3&nbsp;mg (maximum 0.04&nbsp;mg/kg).<ref>* {{cite book | vauthors = Bledsoe BE, Porter RS, Cherry RA | year = 2004| title =  Intermediate Emergency Care | chapter = Ch. 3| page = 260 | publisher = Pearson Prentice Hill| location =Upper Saddle River, NJ | isbn = 0-13-113607-0}}</ref>

Atropine is also useful in treating [[Second-degree AV block#Types|second-degree heart block Mobitz type 1 (Wenckebach block)]], and also [[Third-degree AV block|third-degree heart block]] with a high [[Purkinje fibers|Purkinje]] or [[Atrioventricular node|AV-nodal]] [[escape rhythm]].  It is usually not effective in [[Second degree AV block#Type 2 Second-degree AV block|second-degree heart block Mobitz type 2]], and in [[Third-degree AV block|third-degree heart block]] with a low Purkinje or ventricular escape rhythm.{{citation needed|date=January 2022}}

Atropine has also been used to prevent a low heart rate during [[intubation]] of children; however, the evidence does not support this use.<ref>{{cite journal | vauthors = de Caen AR, Berg MD, Chameides L, Gooden CK, Hickey RW, Scott HF, Sutton RM, Tijssen JA, Topjian A, van der Jagt ÉW, Schexnayder SM, Samson RA | title = Part 12: Pediatric Advanced Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care | journal = Circulation | volume = 132 | issue = 18 Suppl 2 | pages = S526-42 | date = November 2015 | pmid = 26473000 | pmc = 6191296 | doi = 10.1161/cir.0000000000000266 }}</ref>

=== Secretions ===
Atropine's actions on the parasympathetic nervous system inhibit salivary and mucous glands. The drug may also inhibit sweating via the sympathetic nervous system.  This can be useful in treating [[hyperhidrosis]], and can prevent the [[death rattle]] of dying patients. Even though atropine has not been officially indicated for either of these purposes by the FDA, it has been used by physicians for these purposes.<ref>{{cite web | title=Death Rattle and Oral Secretions, 2nd ed | website=eperc.mcw.edu | url=http://www.eperc.mcw.edu/EPERC/FastFactsIndex/ff_109.htm | archive-url=https://web.archive.org/web/20140414033606/http://www.eperc.mcw.edu/EPERC/FastFactsIndex/ff_109.htm | archive-date=2014-04-14 | url-status=dead | access-date=2019-10-20}}</ref>

=== Poisonings ===
Atropine acts as an [[Drug antagonism|antagonist]] for [[organophosphate poisoning]] by blocking the action of [[acetylcholine]] at [[muscarinic]] receptors caused by [[organophosphate]] [[insecticide]]s and [[nerve agent]]s, such as [[Tabun (nerve agent)|tabun]] (GA), [[sarin]] (GB), [[soman]] (GD), and [[VX (nerve agent)|VX]]. Troops who are likely to be attacked with [[chemical weapon]]s often carry [[autoinjector]]s with atropine and [[oxime]], for rapid injection into the muscles of the thigh.  In a developed case of nerve gas poisoning, maximum atropinization is desirable. Atropine is often used in conjunction with the oxime [[pralidoxime chloride]].

Some of the nerve agents attack and destroy [[acetylcholinesterase]] by [[phosphorylation]], so the action of acetylcholine becomes excessive and prolonged. Pralidoxime (2-PAM) can be effective against organophosphate poisoning because it can re-cleave this phosphorylation.  Atropine can be used to reduce the effect of the poisoning by blocking muscarinic acetylcholine receptors, which would otherwise be overstimulated, by excessive acetylcholine accumulation.

Atropine or [[diphenhydramine]] can be used to treat [[muscarine]] intoxication.{{medcn|date=March 2022}}

Atropine was added to cafeteria salt shakers in an attempt to poison the staff of [[Radio Free Europe]] during the [[Cold War]].<ref>The Battle Over Hearts and Minds
A Cold War of Spies: Episode 4 |https://www.imdb.com/title/tt27484449/?ref_=ttep_ep4 {{Webarchive|url=https://web.archive.org/web/20240526050120/https://www.imdb.com/title/tt27484449/?ref_=ttep_ep4 |date=2024-05-26 }}</ref><ref>{{cite web | url=https://www.pbsamerica.co.uk/series/a-cold-war-of-spies/#7749 | title=A Cold War of Spies {{pipe}} PBS America {{pipe}} UK | access-date=2024-02-11 | archive-date=2024-02-16 | archive-url=https://web.archive.org/web/20240216182829/https://www.pbsamerica.co.uk/series/a-cold-war-of-spies/#7749 | url-status=live }}</ref>

=== Irinotecan-induced diarrhea ===
Atropine has been observed to prevent or treat [[irinotecan]] induced acute diarrhea.<ref>{{cite journal | vauthors = Yumuk PF, Aydin SZ, Dane F, Gumus M, Ekenel M, Aliustaoglu M, Karamanoglu A, Sengoz M, Turhal SN | title = The absence of early diarrhea with atropine premedication during irinotecan therapy in metastatic colorectal patients | journal = International Journal of Colorectal Disease | volume = 19 | issue = 6 | pages = 609–610 | date = November 2004 | pmid = 15293062 | doi = 10.1007/s00384-004-0613-5 | s2cid = 11784173 }}</ref>

==Side effects==
Adverse reactions to atropine include ventricular [[fibrillation]], supraventricular or [[ventricular tachycardia]], [[Vertigo (medical)|dizziness]], [[nausea]], blurred vision, loss of balance, dilated pupils, [[photophobia]], dry mouth and potentially extreme [[confusion]], deliriant [[hallucination]]s, and [[Psychomotor agitation|excitation]] especially among the elderly. These latter effects are because atropine can cross the [[blood–brain barrier]]. Because of the [[Psychedelics, dissociatives and deliriants|hallucinogenic]] properties, some have used the drug [[recreational drugs|recreationally]], though this is potentially dangerous and often unpleasant.{{medcn|date=December 2015}}

In overdoses, atropine is [[poison]]ous.{{medcn|date=March 2022}} Atropine is sometimes added to potentially addictive drugs, particularly antidiarrhea opioid drugs such as [[diphenoxylate]] or [[difenoxin]], wherein the secretion-reducing effects of the atropine can also aid the antidiarrhea effects.{{medcn|date=March 2022}}

Although atropine treats [[bradycardia]] (slow heart rate) in emergency settings, it can cause paradoxical heart rate slowing when given at very low doses (less than 0.5&nbsp;mg),<ref>{{cite web |url=http://www.uptodate.com/contents/atropine-drug-information |title=Atropine Drug Information|url-access=subscription |website=uptodate.com|access-date=2014-02-02 |url-status=live |archive-url=https://web.archive.org/web/20140220062212/http://www.uptodate.com/contents/atropine-drug-information?source=search_result&search=atropine&selectedTitle=1~150 |archive-date=2014-02-20 }}</ref> presumably as a result of central action in the CNS.<ref>* {{cite book |vauthors=Rang HP, Dale MM, Ritter JM, Flower RJ | year = 2007| title =  Rang and Dale's Pharmacology |url=https://archive.org/details/rangdalespharmac0006dale |url-access=registration | chapter = Ch. 10| page = [https://archive.org/details/rangdalespharmac0006dale/page/153 153] | publisher = Elsevier Churchill Livingstone| isbn = 978-0-443-06911-6}}</ref> One proposed mechanism for atropine's paradoxical bradycardia effect at low doses involves blockade of inhibitory presynaptic muscarinic [[autoreceptor]]s, thereby blocking a system that inhibits the parasympathetic response.<ref>{{cite book| vauthors = Laurence B |title=Goodman & Gilman's Pharmacological Basis of Therapeutics, 12th Edition|date=2010|publisher=McGraw-Hill|isbn=978-0-07-162442-8}}</ref>

Atropine is incapacitating at doses of 10 to 20&nbsp;mg per person. Its LD<sub>50</sub> is estimated to be 453&nbsp;mg per person (by mouth) with a probit slope of 1.8.<ref>{{cite book | vauthors = Goodman E | year = 2010| title =  Historical Contributions to the Human Toxicology of Atropine |veditors=Ketchum J, Kirby R | page = 120 | publisher = Eximdyne| isbn = 978-0-9677264-3-4}}</ref>
The antidote to atropine is [[physostigmine]] or [[pilocarpine]].{{medcn|date=March 2022}}

A common [[mnemonic]] used to describe the physiologic manifestations of atropine overdose is: "hot as a hare, blind as a bat, dry as a bone, red as a beet, and mad as a hatter".<ref name="holzman">{{cite journal | vauthors = Holzman RS | title = The legacy of Atropos, the fate who cut the thread of life | journal = Anesthesiology | volume = 89 | issue = 1 | pages = 241–9 | date = July 1998 | pmid = 9667313 | doi = 10.1097/00000542-199807000-00030 | url = http://www.anesthesiology.org/pt/re/anes/fulltext.00000542-199807000-00030.htm;jsessionid=GSJKLv9vLCdQSmpp6vH3xdhnzWN1hy3s7JqMNFpWkHhLbKJT5vLM!741375937!-949856145!8091!-1#P89 | access-date = 2007-05-21 | s2cid = 28327277 | doi-access = free }} citing J. Arena, Poisoning: Toxicology-Symptoms-Treatments, 3rd edition. Springfield, Charles C. Thomas, 1974, p 345</ref>  These associations reflect the specific changes of warm, dry skin from decreased sweating, blurry vision, decreased lacrimation, vasodilation, and central nervous system effects on [[muscarinic]] receptors, type 4 and 5. This set of symptoms is known as [[toxidrome#Anticholinergic|anticholinergic toxidrome]], and may also be caused by other drugs with anticholinergic effects, such as [[hyoscine hydrobromide]] (scopolamine), [[diphenhydramine]], [[phenothiazine]] [[antipsychotic]]s and [[benztropine]].<ref>{{cite web | url = http://www.intox.org/databank/documents/treat/treate/trt05_e.htm | title = Acute anticholinergic syndrome | vauthors = Szajewski J | year = 1995 | publisher = IPCS Intox Databank | access-date = 2007-05-22| archive-url= https://web.archive.org/web/20070702175337/http://www.intox.org/databank/documents/treat/treate/trt05_e.htm| archive-date= 2 July 2007 | url-status= live}}</ref>

==Contraindications==
It is generally [[contraindicated]] in people with [[glaucoma]], [[pyloric stenosis]], or [[prostatic hypertrophy]], except in doses ordinarily used for preanesthesia.<ref name="Atropine sulfate FDA label">{{cite web |title=Atropine sulfate |url=https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=910cb308-36c6-4330-8f25-45998ec3cde7 |website=dailymed.nlm.nih.gov |publisher=U.S. National Library of Medicine |access-date=30 October 2019 |archive-date=26 July 2020 |archive-url=https://web.archive.org/web/20200726132945/https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=910cb308-36c6-4330-8f25-45998ec3cde7 |url-status=live }}</ref>

==Chemistry==
{{More medical citations needed|date=January 2022}}
Atropine, a [[tropane alkaloid]], is an [[enantiomer]]ic mixture of ''[[Levorotation and dextrorotation|d]]''-[[hyoscyamine]] and ''l''-hyoscyamine,<ref name="PubChem">{{cite web | url=https://pubchem.ncbi.nlm.nih.gov/compound/Atropine_-sulfate-_2_1 | title=PubChem: Atropine, sulfate (2:1) | publisher=National Library of Medicine, National Institutes of Health }}</ref> with most of its physiological effects due to ''l''-hyoscyamine, the 3(''S'')-''endo'' isomer of atropine. Its pharmacological effects are due to binding to [[muscarinic acetylcholine receptor]]s. It is an antimuscarinic agent. Significant levels are achieved in the CNS within 30 minutes to 1 hour and disappear rapidly from the blood with a half-life of 2 hours. About 60% is excreted unchanged in the urine, and most of the rest appears in the urine as hydrolysis and conjugation products. Noratropine (24%), atropine-N-oxide (15%), tropine (2%), and tropic acid (3%) appear to be the major metabolites, while 50% of the administered dose is excreted as apparently unchanged atropine. No conjugates were detectable. Evidence that atropine is present as (+)-hyoscyamine was found, suggesting that stereoselective metabolism of atropine probably occurs.<ref>{{cite journal | vauthors = Van der Meer MJ, Hundt HK, Müller FO | title = The metabolism of atropine in man | journal = The Journal of Pharmacy and Pharmacology | volume = 38 | issue = 10 | pages = 781–4 | date = October 1986 | pmid = 2879005 | doi = 10.1111/j.2042-7158.1986.tb04494.x | s2cid = 27306334 }}</ref> Effects on the iris and ciliary muscle may persist for longer than 72 hours.

The most common atropine compound used in medicine is atropine [[sulfate]] (monohydrate) ({{chem|[[carbon|C]]|17|[[Hydrogen|H]]|23|[[Nitrogen|N]]|[[Oxygen|O]]|3}})<sub>2</sub>·[[sulfuric acid|H<sub>2</sub>SO<sub>4</sub>]]·[[water|H<sub>2</sub>O]], the full chemical name is 1α''H'',5α''H''-tropan-3-α-ol (±)-tropate(ester), sulfate monohydrate.

==Pharmacology==
{{More medical citations needed|date=January 2022}}
In general, atropine counters the "rest and digest" activity of [[gland]]s regulated by the [[parasympathetic nervous system]], producing clinical effects such as increased heart rate and delayed gastric emptying. This occurs because atropine is a competitive, reversible antagonist of the [[muscarinic acetylcholine receptor]]s ([[acetylcholine]] being the main [[neurotransmitter]] used by the parasympathetic nervous system).

Atropine is a [[competitive antagonist]] of the [[muscarinic acetylcholine receptor]] types [[Muscarinic acetylcholine receptor M1|M1]], [[Muscarinic acetylcholine receptor M2|M2]], [[Muscarinic acetylcholine receptor M3|M3]], [[Muscarinic acetylcholine receptor M4|M4]] and [[Muscarinic acetylcholine receptor M5|M5]].<ref>{{cite book | vauthors = Rang HP, Dale MM, Ritter JM, Moore P |title=Pharmacology |page=139 |publisher=Elsevier |year=2003 | isbn = 978-0-443-07145-4 }}</ref> It is classified as an [[anticholinergic drug]] ([[parasympatholytic]]).

In cardiac uses, it works as a nonselective muscarinic acetylcholinergic antagonist, increasing firing of the [[sinoatrial node]] (SA) and conduction through the [[atrioventricular node]] (AV) of the [[heart]], opposes the actions of the [[vagus nerve]], blocks [[acetylcholine]] [[receptor (biochemistry)|receptor]] sites, and decreases [[bronchial]] [[secretion]]s.

In the eye, atropine induces [[mydriasis]] by blocking the contraction of the circular [[pupillary sphincter]] muscle, which is normally stimulated by acetylcholine release, thereby allowing the radial [[iris dilator muscle]] to contract and dilate the [[pupil]]. Atropine induces [[cycloplegia]] by paralyzing the [[ciliary muscle]]s, whose action inhibits accommodation to allow accurate refraction in children, helps to relieve pain associated with [[iridocyclitis]], and treats ciliary block (malignant) [[glaucoma]].

The vagus (parasympathetic) nerves that innervate the heart release acetylcholine (ACh) as their primary neurotransmitter. ACh binds to muscarinic receptors (M2) that are found principally on cells comprising the sinoatrial (SA) and atrioventricular (AV) nodes. Muscarinic receptors are coupled to the [[Gi alpha subunit|G<sub>i</sub> subunit]]; therefore, vagal activation decreases cAMP. Gi-protein activation also leads to the activation of [[KACh channel]]s that increase potassium efflux and hyperpolarizes the cells.

Increases in vagal activities to the SA node decrease the firing rate of the pacemaker cells by decreasing the slope of the pacemaker potential (phase 4 of the action potential); this decreases heart rate (negative chronotropy). The change in phase 4 slope results from alterations in potassium and calcium currents, as well as the slow-inward sodium current that is thought to be responsible for the pacemaker current (If). By hyperpolarizing the cells, vagal activation increases the cell's threshold for firing, which contributes to the reduction in the firing rate. Similar electrophysiological effects also occur at the AV node; however, in this tissue, these changes are manifested as a reduction in impulse conduction velocity through the AV node (negative dromotropy). In the resting state, there is a large degree of vagal tone in the heart, which is responsible for low resting heart rates.

There is also some vagal innervation of the atrial muscle, and to a much lesser extent, the ventricular muscle. Vagus activation, therefore, results in modest reductions in atrial contractility (inotropy) and even smaller decreases in ventricular contractility.

Muscarinic receptor antagonists bind to muscarinic receptors thereby preventing ACh from binding to and activating the receptor. By blocking the actions of ACh, muscarinic receptor antagonists very effectively block the effects of vagal nerve activity on the heart. By doing so, they increase heart rate and conduction velocity.

== History ==
[[File:Atropa bella-donna0.jpg|thumb|''Atropa belladonna'']]

The name ''atropine'' was coined in the 19th century, when pure extracts from the belladonna plant ''[[Atropa belladonna]]'' were first made.<ref>''Goodman and Gilman's Pharmacological Basis of Therapeutics'', q.v. "Muscarinic receptor antagonists - History", p. 163 of the 2001 edition.</ref> The medicinal use of preparations from [[Solanaceae|plants in the nightshade family]] is much older however. ''Mandragora'' ([[mandrake]]) was described by [[Theophrastus]] in the fourth century BC for the treatment of wounds, gout, and sleeplessness, and as a love [[potion]]. By the first century AD [[Dioscorides]] recognized wine of mandrake as an [[anaesthetic]] for treatment of pain or sleeplessness, to be given before surgery or cautery.<ref name="holzman" />  The use of nightshade preparations for anesthesia, often in combination with [[opium]], persisted throughout the Roman and Islamic Empires and continued in Europe until superseded in the 19th century by modern anesthetics.{{citation needed|date=January 2022}}

Atropine-rich extracts from the Egyptian [[henbane]] plant (another nightshade) were used by [[Cleopatra]] in the last century B.C. to dilate the [[pupils]] of her eyes, in the hope that she would appear more alluring{{citation needed|date=May 2025}}. Likewise, it is widely claimed that in the [[Renaissance]], women used the juice of the berries of the nightshade ''[[Atropa belladonna]]'' to enlarge their pupils for cosmetic reasons. However, primary records of this practice are not known, and the claim may have originated much later by conflating records of actual cosmetic use (for complexion) with the mydriastic properties of atropine. A source from the late 19th century<ref name="harris">{{cite book | title=The Homoeopathic Vade Mecum of Modern Medicine and Surgery: For the Use of Junior Practitioners, Students, Clergymen, Missionaries, Heads of Families, Etc | author=Edward Harris Ruddock | edition=2 | publisher=[[Jarrold and Sons]] |year=1867 | pages=503–508 | url=https://books.google.com/books?id=sxADAAAAQAAJ&q=belladonna+atropos+date:0-1900&pg=PA502 | author-link=Edward Harris Ruddock }}</ref> claims that the practice was also current in Paris.

The pharmacological study of ''belladonna'' extracts was begun by the [[Germany|German]] [[chemist]] [[Friedlieb Ferdinand Runge]] (1795–1867). In 1831, the German pharmacist Heinrich F. G. Mein (1799-1864)<ref>{{cite web | title=Heinrich Friedrich Georg Mein| website=ostfriesischelandschaft.de  | url=http://www.ostfriesischelandschaft.de/fileadmin/php/side.php?news_id=997&part_id=0&navi=11 | archive-url=https://web.archive.org/web/20130511031004/http://www.ostfriesischelandschaft.de/fileadmin/php/side.php?news_id=997&part_id=0&navi=11 | archive-date=2013-05-11 | url-status=unfit | language=de | access-date=2019-10-20}}</ref> succeeded in preparing a pure crystalline form of the active substance, which was named ''atropine''.<ref>{{cite book| author = von dem Apotheker Mein zu Neustadt-Göders |title=Annalen der Pharmacie|url=https://books.google.com/books?id=tT09AAAAcAAJ&pg=PA67|edition=1st|volume=6|year=1833|language=de|pages=67–72|chapter=Ueber die Darstellung des Atropins in weissen Kristallen|trans-chapter=On the preparation of atropine as white crystals|access-date=2016-01-05|archive-date=2016-05-15|archive-url=https://web.archive.org/web/20160515150443/https://books.google.com/books?id=tT09AAAAcAAJ&pg=PA67|url-status=live}}</ref><ref>Atropine was also independently isolated in 1833 by Geiger and Hesse:
*  {{cite book|vauthors=Geiger, Hesse|title=Annalen der Pharmacie|url=https://books.google.com/books?id=pz09AAAAcAAJ&pg=PA43|volume=5|year=1833|language=de|pages=43–81|chapter=Darstellung des Atropins|trans-chapter=Preparation of atropine|access-date=2016-01-05|archive-date=2016-05-14|archive-url=https://web.archive.org/web/20160514231012/https://books.google.com/books?id=pz09AAAAcAAJ&pg=PA43|url-status=live}}
*  {{cite book|vauthors=Geiger, Hesse|title=Annalen der Pharmacie|url=https://books.google.com/books?id=tT09AAAAcAAJ&pg=PA44|volume=6|year=1833|language=de|pages=44–65|chapter=Fortgesetzte Versuche über Atropin|trans-chapter=Continued experiments on atropine|access-date=2016-01-05|archive-date=2016-06-10|archive-url=https://web.archive.org/web/20160610162825/https://books.google.com/books?id=tT09AAAAcAAJ&pg=PA44|url-status=live}}</ref> The substance was first synthesized by German chemist [[Richard Willstätter]] in 1901.<ref>See:
* {{cite journal | vauthors = Willstätter R | year = 1901 | title = Synthese des Tropidins |trans-title=Synthesis of tropidine | url = http://gallica.bnf.fr/ark:/12148/bpt6k907582/f243.image.langEN | journal = Berichte der Deutschen Chemischen Gesellschaft zu Berlin | volume = 34 | pages = 129–144 | doi = 10.1002/cber.19010340124 | url-status = live | archive-url = https://web.archive.org/web/20130301050307/http://gallica.bnf.fr/ark%3A/12148/bpt6k907582/f243.image.langEN | archive-date = 2013-03-01 |language=de}}
* {{cite journal | vauthors = Willstätter R | year = 1901 | title = Umwandlung von Tropidin in Tropin |trans-title=Conversion of tropidine into tropine | url = http://visualiseur.bnf.fr/ark:/12148/bpt6k90759d | journal = Berichte der Deutschen Chemischen Gesellschaft zu Berlin | volume = 34 | issue =  2| pages = 3163–3165 | doi = 10.1002/cber.190103402289 | url-status = live | archive-url = https://web.archive.org/web/20130126014141/http://visualiseur.bnf.fr/ark%3A/12148/bpt6k90759d | archive-date = 2013-01-26 |language=de }}</ref>

== Natural sources ==
Atropine is found in many members of the family [[Solanaceae]]. The most commonly found sources are ''[[Atropa belladonna]]'' (the [[deadly nightshade]]), ''[[Datura innoxia]]'', ''[[Datura wrightii|D. wrightii]]'',  ''[[Datura metel|D. metel]]'', and ''[[Datura stramonium|D. stramonium]]''. Other sources include members of the genera ''[[Brugmansia]]'' (angel's trumpets) and ''[[Hyoscyamus]]''.<ref name="PubChem"></ref>

==Synthesis==
Atropine can be synthesized by the reaction of [[tropine]] with [[tropic acid]] in the presence of [[hydrochloric acid]].

===Biosynthesis===

The biosynthesis of atropine starting from [[Phenylalanine|''l''-phenylalanine]] first undergoes a [[transamination]] forming [[phenylpyruvic acid]] which is then reduced to phenyl-lactic acid.<ref name=dewick>{{cite book| vauthors = Dewick PM |title=Medicinal Natural Products: A Biosynthetic Approach|edition=3rd|date=9 March 2009|publisher=A John Wiley & Sons|location=Chichester|isbn=978-0-470-74167-2}}</ref>  Coenzyme A then couples phenyl-lactic acid with [[tropine]] forming [[littorine]], which then undergoes a radical rearrangement initiated with a [[P450|P450 enzyme]] forming hyoscyamine aldehyde.<ref name=dewick/>  A [[dehydrogenase]] then reduces the aldehyde to a primary alcohol making (−)-hyoscyamine, which upon racemization forms atropine.<ref name=dewick/>

==Society and culture==
The species name "belladonna" ('beautiful woman' in [[Italian language|Italian]]) comes from the original use of deadly nightshade to dilate the pupils of the eyes for cosmetic effect. Both atropine and the genus name for deadly nightshade derive from [[Atropos]], one of the three [[Moirai|Fates]] who, according to Greek mythology, chose how a person was to die.<ref name="holzman" />

=== Legal status ===
In March 2025, the [[Committee for Medicinal Products for Human Use]] of the [[European Medicines Agency]] adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Ryjunea, intended for slowing the progression of myopia in children aged 3 to 14 years.<ref name="Ryjunea EPAR" /> The applicant for this medicinal product is Santen Oy.<ref name="Ryjunea EPAR">{{cite web | title=Ryjunea EPAR | website=European Medicines Agency (EMA) | date=27 March 2025 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/ryjunea | access-date=28 March 2025}}</ref>

== References ==
{{Reflist}}

== External links ==
* {{Commons category-inline}}

{{Ancient anaesthesia}}
{{Drugs for functional gastrointestinal disorders}}
{{Emergency medicine}}
{{Hallucinogens}}
{{Mydriatics and cycloplegics}}
{{Opthalmologicals}}
{{Muscarinic acetylcholine receptor modulators}}
{{Authority control}}
{{Portal bar|Medicine}}

[[Category:Antidotes]]
[[Category:Chemical substances for emergency medicine]]
[[Category:Deliriants]]
[[Category:Entheogens]]
[[Category:Esters]]
[[Category:Drugs developed by Pfizer]]
[[Category:Glycine receptor agonists]]
[[Category:M1 receptor antagonists]]
[[Category:M2 receptor antagonists]]
[[Category:M3 receptor antagonists]]
[[Category:M4 receptor antagonists]]
[[Category:M5 receptor antagonists]]
[[Category:Medical mnemonics]]
[[Category:Oneirogens]]
[[Category:Ophthalmology drugs]]
[[Category:Plant toxins]]
[[Category:Secondary metabolites]]
[[Category:Tropane alkaloids]]
[[Category:Tropane alkaloids found in Solanaceae]]
[[Category:World Health Organization essential medicines]]
[[Category:Wikipedia medicine articles ready to translate]]