Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Scopolamine: Difference between pages

{{Short description|Tropane alkaloid & anticholinergic drug}}{{For|the medication used to treat abdominal pain|Hyoscine butylbromide}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

{{redirect|Hyoscine|Other uses}}

{{redirect|Devil's Breath|the novel|The Devil's Breath{{!}}''The Devil's Breath''}}

{{Use dmy dates|date=February 2022}}

{{Infobox drug

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 464387972

| image = L-Scopolamin.svg

| width = 200

| alt =

| caption =

| image2 = Scopolamine structure.png

| width2 =

| alt2 =

<!-- Clinical data -->

| pronounce =

| tradename = Transdermscop, Kwells, others

| Drugs.com = {{drugs.com|monograph|scopolamine}}

| MedlinePlus = a682509

| DailyMedID = Scopolamine

| pregnancy_AU = B2

| pregnancy_AU_comment =

| pregnancy_category =

| routes_of_administration = [[Oral administration|By mouth]], [[transdermal patch|transdermal]], [[ophthalmic drug administration|ophthalmic]], [[Subcutaneous injection|subcutaneous]], [[intravenous]], [[sublingual]], [[rectal]], [[Buccal administration|buccal]], [[transmucosal]], [[intramuscular]]

| class = {{plainlist|

* [[Antimuscarinic]]

* [[Deliriant]]

* [[Antiemetic]]

* [[Amnestic]]}}

| ATC_prefix = A04

| ATC_suffix = AD01

| ATC_supplemental = {{ATC|N05|CM05}}, {{ATC|S01|FA02}}

<!-- Legal status -->

| legal_AU = S4

| legal_AU_comment = /&nbsp;S2<ref>{{cite web | title=Poisons Standard October 2020 | website=Federal Register of Legislation | date=30 September 2020 | url=https://www.legislation.gov.au/Details/F2020L01255 | access-date=23 October 2020}}</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 = POM

| legal_UK_comment = /&nbsp;P<ref>{{cite web | title=Hyoscine Hydrobromide 400 micrograms/ml Solution for Injection - Summary of Product Characteristics (SmPC) | website=(emc) | url=https://www.medicines.org.uk/emc/product/9655/smpc | access-date=23 October 2020 | archive-date=27 October 2020 | archive-url=https://web.archive.org/web/20201027041325/https://www.medicines.org.uk/emc/product/9655/smpc | url-status=dead }}</ref><ref>{{cite web | title=Kwells 300 microgram tablets - Summary of Product Characteristics (SmPC) | website=(emc) | url=https://www.medicines.org.uk/emc/product/250/smpc | access-date=23 October 2020 | archive-date=26 October 2020 | archive-url=https://web.archive.org/web/20201026064949/https://www.medicines.org.uk/emc/product/250/smpc | url-status=dead }}</ref>

| legal_US = Rx-only

| legal_US_comment = <ref name="Transderm Scop FDA label">{{cite web | title=Transderm Scop- scopolamine patch, extended release | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7192d89d-ea4b-42b0-b8c1-e7fd41be8a0a | access-date=4 February 2022}}</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 =

| protein_bound =

| metabolism = [[Liver]]

| metabolites =

| onset =

| elimination_half-life = 4.5 hours<ref name="pmid2762223">{{cite journal | vauthors = Putcha L, Cintrón NM, Tsui J, Vanderploeg JM, Kramer WG | title = Pharmacokinetics and oral bioavailability of scopolamine in normal subjects | journal = Pharmaceutical Research | volume = 06 | issue = 6 | pages = 481–485 | date = June 1989 | pmid = 2762223 | doi = 10.1023/A:1015916423156 | s2cid = 27507555 }}</ref>

| duration_of_action =

| excretion = [[Kidney]]

<!-- Identifiers -->

| index2_label = as salt

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 51-34-3

| CAS_supplemental =

| PubChem = 5184

| IUPHAR_ligand = 330

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB00747

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 10194106

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = DL48G20X8X

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D00138

| KEGG2_Ref = {{keggcite|correct|kegg}}

| KEGG2 = D02071

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 16794

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 569713

| NIAID_ChemDB =

| PDB_ligand =

| synonyms = Hyoscine<ref name=AHFS2016/>

<!-- Chemical and physical data -->

| IUPAC_name = (–)-(''S'')-3-Hydroxy-2-phenylpropionic acid (1''R'',2''R'',4''S'',5''S'',7''α'',9''S'')-9-methyl-3-oxa-9-azatricyclo[3.3.1.0^2,4]non-7-yl ester

| C = 17 | H = 21 | N = 1 | O = 4

| SMILES = OC[C@H](c1ccccc1)C(=O)O[C@@H]2C[C@H]3N(C)[C@@H](C2)[C@@H]4O[C@H]34

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C17H21NO4/c1-18-13-7-11(8-14(18)16-15(13)22-16)21-17(20)12(9-19)10-5-3-2-4-6-10/h2-6,11-16,19H,7-9H2,1H3/t11-,12-,13-,14+,15-,16+/m1/s1

| StdInChI_comment =

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = STECJAGHUSJQJN-FWXGHANASA-N

| density =

| density_notes =

| melting_point =

| melting_high =

| melting_notes =

| boiling_point =

| boiling_notes =

| solubility =

| sol_units =

| specific_rotation =

<!-- Definition and medical uses -->

'''Scopolamine''', also known as '''hyoscine''',<ref name=Huo2001>{{cite book| vauthors = Juo PS |title=Concise Dictionary of Biomedicine and Molecular Biology.|date=2001|publisher=CRC Press|location=Hoboken|isbn=978-1-4200-4130-9|page=570|edition=2nd|url=https://books.google.com/books?id=Y4DLBQAAQBAJ&pg=PA570|url-status=live|archive-url=https://web.archive.org/web/20170910183136/https://books.google.com/books?id=Y4DLBQAAQBAJ&pg=PA570|archive-date=10 September 2017}}</ref> '''hyoscine hydrobromide,''' or '''Devil's Breath''',<ref>{{cite news | vauthors = Duffy R | title=Colombian Devil's Breath | website=[[Vice (magazine)|Vice]] | date=23 July 2007 | url=https://www.vice.com/en/article/kw3kam/colombian-devil-s-breath-1-of-2 | access-date=3 February 2022}}</ref> is a [[Natural product|natural]] or [[chemical synthesis|synthetically]] produced [[tropane alkaloid]] and [[anticholinergic]] [[drug]] that is used as a medication to treat [[motion sickness]]<ref>{{Cite web |date=2022-10-24 |title=About hyoscine hydrobromide |url=https://www.nhs.uk/medicines/hyoscine-hydrobromide/about-hyoscine-hydrobromide/ |access-date=2023-03-14 |website=nhs.uk |language=en}}</ref> and [[postoperative nausea and vomiting]].<ref name="Springer Science & Business Media">{{cite book | vauthors = Osbourn AE, Lanzotti V |title=Plant-derived Natural Products: Synthesis, Function, and Application |date=2009 |publisher=Springer Science & Business Media |isbn=978-0-387-85498-4 |page=5 |url=https://books.google.com/books?id=Y8SpVXEng4QC&pg=PA6 |url-status=live |archive-url=https://web.archive.org/web/20170910183136/https://books.google.com/books?id=Y8SpVXEng4QC&pg=PA6 |archive-date=10 September 2017 }}</ref><ref name=AHFS2016/> It is also sometimes used before surgery to decrease [[saliva]].<ref name=AHFS2016/> When used by injection, effects begin after about 20&nbsp;minutes and last for up to 8&nbsp;hours.<ref name=AHFS2016/> It may also be used orally and as a [[transdermal patch]] since it has been long known to have transdermal [[bioavailability]].<ref name=AHFS2016>{{cite web |title=Scopolamine|url=https://www.drugs.com/monograph/scopolamine.html|publisher=The American Society of Health-System Pharmacists |access-date=8 December 2016|url-status=live |archive-url=https://web.archive.org/web/20161007123115/https://www.drugs.com/monograph/scopolamine.html |archive-date=7 October 2016}}</ref><ref name="W.B. Saunders">{{cite book| vauthors = Sollmann T | title= A Manual of Pharmacology and Its Applications to Therapeutics and Toxicology | edition=8th| publisher= W.B. Saunders| place= Philadelphia and London | year= 1957}}</ref>

Scopolamine is in the [[antimuscarinic]] family of drugs and works by blocking some of the effects of [[acetylcholine]] within the [[nervous system]].<ref name=AHFS2016/><!-- History, society, and culture -->

Scopolamine was first written about in 1881 and started to be used for [[anesthesia]] around 1900.<ref name=Keys>{{cite book | vauthors = Keys TE |title=The history of surgical anesthesia |date=1996 |publisher=Wood Library, Museum of Anesthesiology |location=Park Ridge, Ill. |isbn=978-0-9614932-7-1 |page=48ff |edition=Reprint |url=https://www.woodlibrarymuseum.org/wp-content/uploads/e-books/w0012pdf.PDF}}</ref><ref name=Fis2006>{{cite book| vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006|publisher=John Wiley & Sons|isbn=978-3-527-60749-5|page=551|url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA551}}</ref> Scopolamine is also the main active component produced by certain plants of the [[solanaceae|nightshade family]], which historically have been used as [[psychoactive]] drugs, known as ''[[deliriants]]'', due to their antimuscarinic-induced [[Hallucinogens#Deliriants|hallucinogenic]] effects in higher doses.<ref name="Springer Science & Business Media"/> In these contexts, its mind-altering effects have been utilized for [[Recreational drug use|recreational]] and [[occult]] purposes.<ref name="Kennedy 2014">{{cite book | vauthors = Kennedy DO |year=2014 |chapter=The Deliriants - The Nightshade (''Solanaceae'') Family |chapter-url=https://books.google.com/books?id=YUNDAgAAQBAJ&pg=PA131 |title=Plants and the Human Brain |location=[[New York City|New York]] |publisher=[[Oxford University Press]] |pages=131–137 |isbn=978-0-19-991401-2 |lccn=2013031617 |access-date=2021-09-17 |archive-date=2021-09-17 |archive-url=https://web.archive.org/web/20210917082513/https://books.google.com/books?id=YUNDAgAAQBAJ&pg=PA131 |url-status=live }}</ref><ref name= "Uribe_et_al_2005"/><ref name="Raetsch">{{Cite book|title=The encyclopedia of psychoactive plants: ethnopharmacology and its applications| vauthors = Raetsch C |publisher=US: Park Street Press| year= 2005|pages=277–282}}</ref> The name "scopolamine" is derived from one type of nightshade known as ''[[Scopolia]]'', while the name "hyoscine" is derived from another type known as ''[[Hyoscyamus niger]]'', or black henbane.<ref name=Chambers>{{cite book|title=The Chambers Dictionary|year=1998|publisher=Allied Publishers|isbn=978-81-86062-25-8|pages=788, 1480}}</ref><ref name="Cattell1910">{{cite book | vauthors = Cattell HW |title=Lippincott's new medical dictionary: a vocabulary of the terms used in medicine, and the allied sciences, with their pronunciation, etymology, and signification, including much collateral information of a descriptive and encyclopedic character |url=https://books.google.com/books?id=W_hEAAAAQAAJ&pg=PA435 |access-date=25 February 2012 |year=1910 |publisher=Lippincott |page=435 |url-status=live |archive-url=https://web.archive.org/web/20170910183136/https://books.google.com/books?id=W_hEAAAAQAAJ&pg=PA435 |archive-date=10 September 2017 }}</ref> It is on the [[World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO }}</ref>

== Medical uses ==

Scopolamine has a number of formal uses in modern medicine where it is used in its isolated form and in low doses to treat:<ref name="BNF">{{cite book |isbn = 978-0-85711-084-8 |title = British National Formulary (BNF) | author = Joint Formulary Committee |year = 2013 |publisher = Pharmaceutical Press |location = London, UK |edition = 65 |pages = [https://archive.org/details/bnf65britishnati0000unse/page/49 49, 266, 822, 823] |url = https://archive.org/details/bnf65britishnati0000unse/page/49 }}</ref><ref name="AMH">{{cite book | veditors = Rossi S |isbn = 978-0-9805790-9-3 |title = Australian Medicines Handbook |place = Adelaide |publisher = The Australian Medicines Handbook Unit Trust |year = 2013 |edition = 2013}}</ref>

* [[Postoperative nausea and vomiting]].

* [[Motion sickness]], including [[sea sickness]], leading to its use by [[scuba diver]]s (where it is often applied as a transdermal patch behind the ear)<ref name="pmid1853467">{{cite journal | vauthors = Bitterman N, Eilender E, Melamed Y | title = Hyperbaric oxygen and scopolamine | journal = Undersea Biomedical Research | volume = 18 | issue = 3 | pages = 167–174 | date = May 1991 | pmid = 1853467 | url = http://archive.rubicon-foundation.org/2573 | url-status = usurped | access-date = 13 August 2008 | archive-url = https://web.archive.org/web/20080820004729/http://archive.rubicon-foundation.org/2573 | archive-date = 20 August 2008 }}</ref><ref name="pmid3363755">{{cite journal | vauthors = Williams TH, Wilkinson AR, Davis FM, Frampton CM | title = Effects of transcutaneous scopolamine and depth on diver performance | journal = Undersea Biomedical Research | volume = 15 | issue = 2 | pages = 89–98 | date = March 1988 | pmid = 3363755 | url = http://archive.rubicon-foundation.org/2495 | url-status = usurped | archive-url = https://web.archive.org/web/20080820005139/http://archive.rubicon-foundation.org/2495 | archive-date = 20 August 2008 }}</ref><ref>{{cite journal | vauthors = Williams TH, Wilkinson AR, Davis FM, Frampton CM | title = Effects of transcutaneous scopolamine and depth on diver performance | journal = Undersea Biomedical Research | volume = 15 | issue = 2 | pages = 89–98 | date = March 1988 | pmid = 3363755 }}</ref><ref>{{cite web |title=Motion Sickness |url=https://dan.org/health-medicine/health-resources/diseases-conditions/motion-sickness/ |website=Divers Alert Network}}</ref>

* [[Gastrointestinal tract|Gastrointestinal]] spasms

* [[Renal tract|Renal]] or [[Biliary tract|biliary]] spasms

* Aid in gastrointestinal [[radiology]] and [[endoscopy]]

* [[Irritable bowel syndrome]]

* [[Clozapine]]-induced [[hypersalivation|drooling]]

* [[Bowel]] [[colic]]

* Eye [[inflammation]]<ref>{{cite web |title=scopolamine solution - ophthalmic, Isopto |url=https://www.medicinenet.com/scopolamine_drops-ophthalmic/article.htm |website=MedicineNet.com |access-date=12 February 2019}}</ref>

It is sometimes used as a [[premedication]], especially to reduce [[respiratory tract]] [[secretions]] in [[surgery]], most commonly by [[Injection (medicine)|injection]].<ref name = BNF/><ref name = AMH/> Common side effects include sleepiness, [[blurred vision]], [[dilated pupils]], and dry mouth.<ref name=AHFS2016/> It is not recommended in people with angle-closure [[glaucoma]] or [[bowel obstruction]].<ref name=AHFS2016/> Whether its use during pregnancy is safe remains unclear, and use during [[breastfeeding]] is still cautioned by health professionals and manufacturers of the drug.<ref name="Briggs 1994">{{cite book | vauthors = Briggs GG, Freeman RK, Yaffe SJ | chapter = Scopolamine |title=Drugs in Pregnancy and Lactation | chapter-url=https://archive.org/details/drugsinpregnancy00gera/page/777 |date=1994 |publisher=Williams and Wilkins |location=Baltimore, Maryland |pages=777–778 |isbn=978-0-683-01060-2 }}</ref>

===Breastfeeding===

Scopolamine enters [[breast milk]] by [[secretion]]. Although no human studies exist to document the safety of scopolamine while nursing, the manufacturer recommends that caution be taken if scopolamine is administered to a breastfeeding woman.<ref name="Briggs 1994"/>

===Elderly===

The likelihood of experiencing adverse effects from scopolamine is increased in the elderly, relative to younger people. This phenomenon is especially true for older people who are also on several other medications. Scopolamine use should be avoided in this age group because of these potent anticholinergic adverse effects, which have also been linked to an increased risk for [[dementia]].<ref>{{cite web |url = http://www.alzheimers.org.uk/site/scripts/news_article.php?newsID=2300 |title = Study suggests link between long-term use of anticholinergics and dementia risk |publisher = [[Alzheimer's Society]] |date = 26 January 2015 |access-date = 17 February 2015 |url-status = live |archive-url = https://web.archive.org/web/20151112115547/https://www.alzheimers.org.uk/site/scripts/news_article.php?newsID=2300 |archive-date = 12 November 2015 }}</ref><ref>{{cite journal | vauthors = Flicker C, Ferris SH, Serby M | title = Hypersensitivity to scopolamine in the elderly | journal = Psychopharmacology | volume = 107 | issue = 2–3 | pages = 437–441 | date = 1992 | pmid = 1615141 | doi = 10.1007/bf02245172 | s2cid = 29065240 }}</ref>

==Adverse effects==

Adverse effect incidence:<ref name="Transderm Scop FDA label" /><ref name=TGAin>{{cite web|title=DBL HYOSCINE INJECTION BP|date=30 January 2012|work=TGA eBusiness Services|publisher=Hospira Australia Pty Ltd|access-date=22 October 2013|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2009-PI-00398-3|url-status=live|archive-url=https://web.archive.org/web/20170330184646/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2009-PI-00398-3|archive-date=30 March 2017}}</ref><ref name=EMCBut>{{cite web|title=Buscopan Tablets - Summary of Product Characteristics (SPC)|work=electronic Medicines Compendium|publisher=Boehringer Ingelheim Limited|date=11 September 2013|access-date=22 October 2013|url=http://www.medicines.org.uk/emc/medicine/282/SPC/Buscopan+Tablets/|url-status=live|archive-url=https://web.archive.org/web/20131023062458/http://www.medicines.org.uk/emc/medicine/282/SPC/Buscopan+Tablets/|archive-date=23 October 2013}}</ref><ref name=EMChyd>{{cite web |title=Kwells 300 microgram tablets - Summary of Product Characteristics |date=7 January 2008 |access-date=22 October 2013 |work=electronic Medicines Compendium |publisher=Bayer plc |url=http://www.medicines.org.uk/emc/medicine/18845/SPC/Kwells+300+microgram+tablets/ |url-status=live |archive-url=https://web.archive.org/web/20131023061617/http://www.medicines.org.uk/emc/medicine/18845/SPC/Kwells+300+microgram+tablets/ |archive-date=23 October 2013 }}</ref>

Uncommon (0.1–1% incidence) adverse effects include:

* [[Dry mouth]]

* [[Hypohidrosis|Anhidrosis]] (reduced ability to sweat to cool off)

* [[Tachycardia]] (usually occurs at higher doses and is succeeded by bradycardia)

* [[Bradycardia]]

* [[Urticaria]] (hives)

* [[Pruritus]] (itching)

Rare (<0.1% incidence) adverse effects include:

* [[Constipation]]

* [[Urinary retention]]

* [[Hallucination]]s

* Agitation

* Confusion

* Restlessness

* [[Seizure]]s

Unknown frequency adverse effects include:

* [[Anaphylactic shock]] or [[Anaphylactic reactions|reactions]]

* [[Dyspnea]] (shortness of breath)

* Rash

* [[Erythema]]

* Other hypersensitivity reactions

* [[Blurred vision]]

* [[Mydriasis]] (dilated pupils)

* [[Drowsiness]]

* [[Dizziness]]

* [[Somnolence]]

* [[Death]]

==Overdose==

[[Physostigmine]], a cholinergic drug that readily crosses the [[blood–brain barrier]], has been used as an antidote to treat the [[central nervous system depression]] symptoms of a scopolamine overdose.<ref>{{cite book| veditors = Barash PG, Cahalan M, Cullen BF, Stock MC, Stoelting RK |title= Clinical anesthesia |year=2009 |publisher=Wolters Kluwer/Lippincott Williams & Wilkins |location=Philadelphia |isbn=978-0-7817-8763-5 |page=346 |edition=6th }}</ref> Other than this [[supportive treatment]], [[gastric lavage]] and induced [[emesis]] (vomiting) are usually recommended as treatments for oral overdoses.<ref name = EMChyd/> The symptoms of overdose include:<ref name = EMCBut/><ref name = EMChyd/>

* Tachycardia

* [[Heart arrhythmia|Arrhythmia]]

* Blurred vision

* [[Photophobia]]

* [[Urinary retention]]

* [[Drowsiness]] or [[paradoxical reaction]], which can present with [[hallucinations]]

* [[Cheyne-Stokes]] respiration

* Dry mouth

* [[Erythema|Skin reddening]]

* Inhibition of [[gastrointestinal motility]]

== Interactions ==

Due to interactions with metabolism of other drugs, scopolamine can cause significant unwanted side effects or unpredictable [[Drug synergy|synergies]] when taken with other medications or compounds. Specific attention should be paid to other medications in the same [[Pharmacology|pharmacologic]] class as scopolamine, also known as [[anticholinergic]]s.

The following compounds could also potentially interact with the metabolism of scopolamine: receptor-binding [[analgesic]]/pain medication such as [[gabapentinoids]] or [[opioids]], [[ethanol]], [[cannabinoids]], [[zolpidem]], [[thiazide diuretics]], [[nicotine]], [[benzodiazepines]], [[buprenorphine]], and especially anticholinergic drugs such as [[Tiotropium bromide|tiotropium]], [[diphenhydramine]], [[dimenhydrinate]], etc. Nicotine in particular likely has a counteracting effect on the effects of scopolamine due to its opposing effect on acetylcholine signaling.{{Citation needed|date=May 2021}}

==Route of administration==

Scopolamine can be taken [[Oral administration|by mouth]], [[subcutaneous injection|subcutaneously]], [[Ophthalmic drug administration|in the eye]], and [[intravenous]]ly, as well as via a [[transdermal patch]].<ref name="White">{{cite journal | vauthors = White PF, Tang J, Song D, Coleman JE, Wender RH, Ogunnaike B, Sloninsky A, Kapu R, Shah M, Webb T | title = Transdermal scopolamine: an alternative to ondansetron and droperidol for the prevention of postoperative and postdischarge emetic symptoms | journal = Anesthesia and Analgesia | volume = 104 | issue = 1 | pages = 92–96 | date = January 2007 | pmid = 17179250 | doi = 10.1213/01.ane.0000250364.91567.72 | s2cid = 44784425 | doi-access = free }}</ref>

==Pharmacokinetic==

Scopolamine undergoes first-pass metabolism and about 2.6% is excreted unchanged in urine. [[Grapefruit–drug interactions|Grapefruit juice decreases metabolism]] of scopolamine, consequently increasing plasma concentration.<ref name="pmid16175141">{{cite journal | vauthors = Renner UD, Oertel R, Kirch W | title = Pharmacokinetics and pharmacodynamics in clinical use of scopolamine | journal = Therapeutic Drug Monitoring | volume = 27 | issue = 5 | pages = 655–665 | date = October 2005 | pmid = 16175141 | doi = 10.1097/01.ftd.0000168293.48226.57 | s2cid = 32720769 }}</ref>

==Pharmacodynamics==

The pharmacological effects of scopolamine are mediated through the drug's competitive [[Receptor antagonist|antagonism]] of the peripheral and central [[muscarinic acetylcholine receptor]]s. Scopolamine acts as a nonspecific muscarinic antagonist at all four ([[Muscarinic acetylcholine receptor M1|M₁]], [[Muscarinic acetylcholine receptor M2|M₂]], [[Muscarinic acetylcholine receptor M3|M₃]], and [[Muscarinic acetylcholine receptor M4|M₄]]) receptor sites.<ref>{{cite web|title=Google Scholar|url=https://scholar.google.com/scholar?q=scopolamine+nonselective&btnG=&hl=en&as_sdt=0%2C11|website=scholar.google.com|access-date=16 December 2017}}</ref><ref>{{cite web|title=PDSP Ki Database|url=https://pdsp.unc.edu/databases/pdsp.php?receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testDDRadio=testDDRadio&testLigandDD=2417&testLigand=&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}</ref>

In doses higher than intended for medicinal use; the hallucinogenic [[alteration of consciousness]], as well as the deliriousness in particular are tied to the compound's activity at the [[Muscarinic acetylcholine receptor M1|M₁]] muscarinic receptor. M₁ receptors are located primarily in the [[central nervous system]] and are involved in perception, attention and cognitive functioning. [[Delirium]] is only associated with the antagonism of [[Postsynaptic potential|postsynaptic]] M₁ receptors and currently other receptor subtypes have not been implicated.<ref name="ReferenceC">{{cite journal | vauthors = Dawson AH, Buckley NA | title = Pharmacological management of anticholinergic delirium - theory, evidence and practice | journal = British Journal of Clinical Pharmacology | volume = 81 | issue = 3 | pages = 516–524 | date = March 2016 | pmid = 26589572 | pmc = 4767198 | doi = 10.1111/bcp.12839 | quote = Delirium is only associated with the antagonism of post‐synaptic M1 receptors and to date other receptor subtypes have not been implicated }}</ref>

Peripheral muscarinic receptors are part of the [[autonomic nervous system]]. M₂ receptors are located in the brain and heart, M₃ receptors are in salivary glands and M₄ receptors are in the brain and lungs.<ref name="ReferenceC"/> Due to the drug's inhibition of various signal transduction pathways, the decrease in [[acetylcholine]] signaling is what leads to many of the cognitive deficits, mental impairments and delirium associated with psychoactive doses. Medicinal effects appear to mostly be tied to activation of the peripheral receptors and only from marginal decreases in acetylcholine signaling.<ref name=":0">{{cite journal | vauthors = Lessenger JE, Feinberg SD | title = Abuse of prescription and over-the-counter medications | journal = Journal of the American Board of Family Medicine | volume = 21 | issue = 1 | pages = 45–54 | date = 2008 | pmid = 18178702 | doi = 10.3122/jabfm.2008.01.070071 | doi-access = free }}</ref>

Although often broadly referred to as simply being 'anticholinergic', [[antimuscarinic]] would be more specific and accurate terminology to use for scopolamine, as, for example, it is not known to block [[nicotinic receptors]].<ref name="ReferenceC"/>

==Biosynthesis in plants==

Scopolamine is among the [[secondary metabolites]] of plants from [[Solanaceae]] (nightshade) family of plants, such as [[henbane]] (''Hyoscyamus niger''), [[jimson weed]] (''[[Datura]]''), [[angel's trumpet]] (''[[Brugmansia]]''), [[deadly nightshade]] (''[[Atropa belladonna|Belladonna]]''), mandrake (''[[Mandragora officinarum]]''), and corkwood (''[[Duboisia]]'').<ref name = "Muranaka_1993">{{cite journal | vauthors = Muranaka T, Ohkawa H, Yamada Y |title = Continuous Production of Scopolamine by a Culture of ''Duboisia leichhardtii'' Hairy Root Clone in a Bioreactor System |journal = Applied Microbiology and Biotechnology |volume = 40 |issue = 2–3 |pages = 219–223 |year = 1993 |doi = 10.1007/BF00170370 |s2cid = 45125074 }}</ref><ref name=Chambers/>

[[File:Tropane alkaloids biochemistry.png|thumb|The biochemistry of tropane class compounds. [[Hyoscyamine]] and scopolamine are present and labeled.]]

The [[biosynthesis]] of scopolamine begins with the [[decarboxylation]] of [[L-ornithine]] to [[putrescine]] by [[ornithine decarboxylase]]. Putrescine is [[Methylation|methylated]] to N-methylputrescine by [[putrescine N-methyltransferase]].<ref name="Ziegler2008">{{cite journal | vauthors = Ziegler J, Facchini PJ | title = Alkaloid biosynthesis: metabolism and trafficking | journal = Annual Review of Plant Biology | volume = 59 | issue = 1 | pages = 735–769 | year = 2008 | pmid = 18251710 | doi = 10.1146/annurev.arplant.59.032607.092730 }}</ref>

A [[putrescine oxidase]] that specifically recognizes methylated putrescine catalyzes the [[deamination]] of this compound to 4-methylaminobutanal, which then undergoes a spontaneous ring formation to N-[[methyl]]-[[pyrrole|pyrrolium]] cation. In the next step, the pyrrolium cation condenses with [[acetoacetic acid]] yielding [[hygrine]]. No [[enzymatic]] activity could be demonstrated to catalyze this reaction. Hygrine further rearranges to [[tropinone]].<ref name="Ziegler2008" />

Subsequently, [[tropinone reductase I]] converts [[tropinone]] to [[tropine]], which condenses with [[phenylalanine]]-derived phenyllactate to [[littorine]]. A [[cytochrome P450]] classified as Cyp80F1<ref>{{cite journal | vauthors = Li R, Reed DW, Liu E, Nowak J, Pelcher LE, Page JE, Covello PS | title = Functional genomic analysis of alkaloid biosynthesis in Hyoscyamus niger reveals a cytochrome P450 involved in littorine rearrangement | journal = Chemistry & Biology | volume = 13 | issue = 5 | pages = 513–520 | date = May 2006 | pmid = 16720272 | doi = 10.1016/j.chembiol.2006.03.005 | doi-access = free }}</ref> oxidizes and rearranges littorine to hyoscyamine [[aldehyde]]. In the final step, [[hyoscyamine]] undergoes [[epoxidation]] catalyzed by [[6beta-hydroxyhyoscyamine epoxidase]] yielding scopolamine.<ref name="Ziegler2008" />

[[File:Scopolamine biosynthesis.svg|center|800px]]

==History==

Plants naturally containing scopolamine such as ''[[Atropa belladonna]]'' (deadly nightshade), ''[[Brugmansia]]'' (angels trumpet), ''[[Datura]]'' (Jimson weed), ''[[Hyoscyamus niger]]'', ''[[Mandragora officinarum]]'', ''[[Scopolia carniolica]]'', ''[[Latua]]'' and ''[[Duboisia myoporoides]]'' have been known about and used for various purposes in both the [[New world|New]] and [[Old World]]s since ancient times.<ref name="Hunziker Genera">Armando T. Hunziker: ''The Genera of Solanaceae''. A.R.G. Gantner Verlag K.G., Ruggell, Liechtenstein 2001. {{ISBN|3-904144-77-4}}</ref><ref name="ReferenceA">Rätsch, Christian, ''The Encyclopedia of Psychoactive Plants: Ethnopharmacology and Its Applications'' pub. Park Street Press 2005</ref><ref>{{cite web|title=Pharmacognosy and Phytochemistry : Drugs Containing Alkaloids|url=http://www.pharmacy180.com/article/duboisia-131/#:~:text=Chemical%20Constituents,%2C%20tigloidine%2C%20valtropine%2C%20tiglyoxytropine.}}</ref> Being one of the earlier alkaloids isolated from plant sources, scopolamine has been in use in its purified forms, such as various salts, including hydrochloride, hydrobromide, hydroiodide, and sulfate, since its official isolation by the German scientist [[Albert Ladenburg]] in 1880,<ref>{{cite journal | vauthors = Ladenburg A |title=Die natürlich vorkommenden mydriatisch wirkenden Alkaloïde |journal=Annalen der Chemie |date=1880 |volume=206 |issue=3 |pages=274–307 |url=https://babel.hathitrust.org/cgi/pt?id=hvd.hx3khy;view=1up;seq=690 |trans-title=The naturally occurring alkaloids that act mydriatically [i.e., to dilate the pupils] |language=de|doi=10.1002/jlac.18812060303 }}; see pp. 299–307.</ref> and as various preparations from its plant-based form since antiquity and perhaps prehistoric times.

Following the description of the structure and activity of scopolamine by Ladenburg, the search for synthetic analogues, and methods for total synthesis, of scopolamine and [[atropine]] in the 1930s and 1940s resulted in the discovery of [[diphenhydramine]], an early antihistamine and the prototype of its chemical subclass of these drugs, and [[pethidine]], the first fully synthetic [[opioid]] [[analgesic]], known as Dolantin and Demerol amongst many other trade names.{{citation needed|date=July 2021}}

In 1899, a Dr. Schneiderlin recommended the use of scopolamine and [[morphine]] for surgical anaesthesia, and it started to be used sporadically for that purpose.<ref name=Keys/><ref name=canadian>{{cite journal | vauthors = | title = Twilight Sleep: the Dammerschlaf of the Germans | journal = Canadian Medical Association Journal | volume = 5 | issue = 9 | pages = 805–808 | date = September 1915 | pmid = 20310688 | pmc = 1584452 }}</ref> The use of this combination in [[obstetric anesthesiology]] (childbirth) was first proposed by Richard von Steinbuchel in 1902 and was picked up and further developed by Carl Gauss in [[Freiburg im Breisgau|Freiburg]], [[Germany]], starting in 1903.<ref name=nyt_invest>{{cite news |title=TWILIGHT SLEEP; Is Subject of a New Investigation|url=https://query.nytimes.com/gst/abstract.html?res=9E05EED8113EE733A05752C3A9679C946496D6CF|newspaper=[[The New York Times]]|date=31 January 1915}}</ref> The method, which was based on a drug [[synergy]] between both scopolamine and morphine came to be known as ''Dämmerschlaf'' ("[[twilight sleep]]") or the "Freiburg method".<ref name=canadian/><ref name=nyt_invest/> It spread rather slowly, and different clinics experimented with different dosages and ingredients. In 1915, the ''Canadian Medical Association Journal'' reported, "the method [was] really still in a state of development".<ref name=canadian/> It remained widely used in the US until the 1960s, when growing [[chemophobia]] and a desire for more [[natural childbirth]] led to its abandonment.<ref name=nyt2>{{cite news | vauthors = Finkbeiner A | title=Labor Dispute. Book review: What a Blessing She Had Chloroform: The Medical and Social Response to the Pain of Childbirth from 1800 to the Present |url=https://www.nytimes.com/1999/10/31/books/labor-dispute.html |work=[[The New York Times]] |date=31 October 1999 }}</ref>

==Society and culture==

===Names===

Hyoscine hydrobromide is the [[international nonproprietary name]], and scopolamine hydrobromide is the [[United States Adopted Name]]. Other names include ''levo''-duboisine, devil's breath, and ''burundanga''.<ref name= "Uribe_et_al_2005">{{cite journal | vauthors = Uribe M, Moreno CL, Zamora A, Acosta P |title=Perfil epidemiológico de la intoxicación con burundanga en la clínica Uribe Cualla S. A. de Bogotá, D. C |language= es |journal=Acta Neurológica Colombiana |volume=21 |issue=3 |pages= 197–201 |date=September 2005 |url= http://www.acnweb.org/acta/2005_21_3_197.pdf |url-status=live |archive-url= https://web.archive.org/web/20161007091943/http://www.acnweb.org/acta/2005_21_3_197.pdf |archive-date=7 October 2016 }}</ref><ref name=Wired-2011-03-03>{{cite magazine |title= Mind controller: What is the 'burundanga' drug? | vauthors = Bell V |date= 3 March 2011 |publication-date= April 2011 |magazine= Wired UK |url= https://www.wired.co.uk/article/mind-controller-1 |url-status= live |archive-url= https://web.archive.org/web/20170811011218/http://www.wired.co.uk/article/mind-controller-1 |archive-date= 11 August 2017 }}</ref>

===Australian bush medicine===

A [[bush medicine]] developed by [[Aboriginal Australians|Aboriginal peoples]] of the [[eastern states of Australia]] from the soft [[Duboisia myoporoides|corkwood]] tree (''[[Duboisia myoporoides]]'') was used by the [[Allies of World War II|Allies]] in World War II to stop soldiers from getting seasick when they sailed across the [[English Channel]] on their way to France during the [[Invasion of Normandy]]. Later, the same substance was found to be usable in the production of scopolamine and [[hyoscyamine]], which are used in [[eye surgery]], and a multimillion-dollar industry was built in [[Queensland]] based on this substance.<ref name=kc2019>{{cite web | title=Visitors to Art of Healing exhibition told how Australian Indigenous bush medicine was given to every allied soldier landing at Normandy on D-Day | website= King's College London | date=7 June 2019 | url= https://www.kcl.ac.uk/news/australian-indigenous-bush-medicine-was-given-to-allied-soldiers-on-d-day | access-date=2 June 2020}}</ref>

===Recreational and religious use===

While it has been occasionally used recreationally for its hallucinogenic properties, the experiences are often unpleasant, mentally and physically. It is also physically dangerous and officially classified as a [[deliriant]] drug, so repeated recreational use is rare.<ref>{{cite book | vauthors = Freye E |title = Pharmacology and Abuse of Cocaine, Amphetamines, Ecstasy and Related Designer Drugs |chapter = Toxicity of Datura Stramonium |publisher = Springer |year = 2010 |location = Netherlands |pages = 217–218 |isbn = 978-90-481-2447-3 |doi = 10.1007/978-90-481-2448-0_34}}</ref> In June 2008, more than 20 people were hospitalized with [[psychosis]] in Norway after ingesting counterfeit [[rohypnol]] tablets containing scopolamine.<ref>{{cite news |url= http://www.aftenposten.no/nyheter/iriks/article2507100.ece |title=Bilsykemedisin i falske rohypnol-tabletter |website= Aftenposten.no |url-status=dead |archive-url=https://web.archive.org/web/20080627021428/http://www.aftenposten.no/nyheter/iriks/article2507100.ece |archive-date=27 June 2008 }}</ref> In January 2018, 9 individuals were hospitalized in Perth, Western Australia, after reportedly ingesting scopolamine.<ref>{{Cite news |url= http://www.abc.net.au/news/2018-01-04/toxicology-results-from-perth-mass-overdose-expected-today/9303330 |title= Perth backpacker overdose linked to common anti-nausea drug|date=4 January 2018|work=ABC News|access-date=4 January 2018}}</ref>

The alkaloid scopolamine, when taken recreationally for its psychoactive effect is usually taken in the form of preparations from plants of the genera ''[[Datura]]'' or ''[[Brugmansia]]'', often by [[adolescents]] or [[young adults]] in order to achieve hallucinations and an [[altered state of consciousness]] induced by [[Muscarinic antagonist|muscarinic antagonism]].<ref>{{cite journal | vauthors = Fatur K, Kreft S | title = Common anticholinergic solanaceaous plants of temperate Europe - A review of intoxications from the literature (1966-2018) | journal = Toxicon | volume = 177 | pages = 52–88 | date = April 2020 | pmid = 32217234 | doi = 10.1016/j.toxicon.2020.02.005 | s2cid = 213559151 }}</ref><ref name='Preissel'>{{cite book | vauthors = Preissel U, Preissel HG | title = ''Brugmansia'' and ''Datura'': Angel's Trumpets and Thorn Apples | publisher = Firefly Books | year = 2002 | location = Buffalo, NY | pages = 106–129 | isbn = 1-55209-598-3 }}</ref> In circumstances such as these, the [[Substance intoxication|intoxication]] is usually built on a [[Drug synergy|synergistic]], but even more toxic mixture of the additional alkaloids in the plants which includes [[atropine]] and [[hyoscyamine]].

Historically, the various plants that produce scopolamine have been used psychoactively for [[Spirituality|spiritual]] and [[magic (supernatural)|magical]] purposes, particularly by witches in western culture and [[indigenous people|indigenous]] groups throughout the [[Americas]] such as [[Native Americans in the United States|Native American]] tribes like the [[Chumash people|Chumash]].<ref name="Raetsch"/><ref name="The Way of the Shaman">{{cite book | vauthors = Harner M |year= 1980| title= The Way of the Shaman|url= https://archive.org/details/wayofshamanguide00harn|url-access= registration| location= New York |publisher= Harper & Row |isbn= 978-0-06-250373-2}}</ref><ref>{{cite book | vauthors = Kuklin A | title = How Do Witches Fly?| publisher = DNA Press |date=February 1999 | isbn = 0-9664027-0-7 }}</ref><ref>{{Cite web|url=https://escholarship.org/content/qt37r1g44r/qt37r1g44r.pdf?t=krnkzn|title = The Datura Cult Among the Chumash; The Journal of California Anthropology}}</ref> When [[entheogenic]] preparations of these plants were used, scopolamine was considered to be the main psychoactive compound and was largely responsible for the hallucinogenic effects, particularly when the preparation was made into a topical ointment, most notably [[flying ointment]].<ref name= "Hansen">Hansen, Harold A. The Witch's Garden pub. Unity Press 1978 {{ISBN|978-0913300473}}</ref>

Scopolamine is reported to be the only active alkaloid within these plants that can effectively be absorbed through the skin to cause effects.<ref name="W.B. Saunders"/> Different recipes for these ointments were explored in [[European witchcraft]] at least as far back as the [[Early Modern]] period and included multiple ingredients to help with the transdermal absorption of scopolamine, such as animal fat, as well as other possible ingredients to counteract its noxious and dysphoric effects.<ref name= "Hansen"/>

In the [[Bible]], there are multiple mentions of [[Mandrake]], a psychoactive and hallucinogenic plant root that contains scopolamine. It was associated with fertility and (sexual) desire where it was yearned for by [[Rachel]], who apparently was "barren" (infertile) but trying to conceive.<ref>{{cite web|title=Genesis 30:14–16 (King James Version)|url=http://www.biblegateway.com/passage/?search=Genesis%2030:14-16&version=KJV|publisher=Bible Gateway|access-date=6 January 2014}}</ref><ref>{{cite web|title=Song of Songs 7:12–13 (King James Version)|url=http://www.biblegateway.com/passage/?search=Song%20of%20Songs%207:12-13&version=KJV|publisher=Bible Gateway|access-date=6 January 2014}}</ref>

===Interrogation===

The effects of scopolamine were studied for use as a [[truth serum]] in interrogations in the early 20th century,<ref>{{cite journal | vauthors = House RE |title = The Use of Scopolamine in Criminology |journal = Texas State Journal of Medicine |volume = 18 |pages = 256–263 |date=September 1922}}<br />

Reprinted in: {{cite journal |doi = 10.2307/1147361 | vauthors = House RE |title = The Use of Scopolamine in Criminology |journal = American Journal of Police Science |volume = 2 |issue = 4 |pages = 328–336 |date = July–August 1931 |jstor = 1147361}}</ref> but because of the side effects, investigations were dropped.<ref>{{cite web | vauthors = Bimmerle G |date=22 September 1993 |title='Truth' Drugs in Interrogation| website= CIA.gov |url= https://www.cia.gov/library/center-for-the-study-of-intelligence/kent-csi/vol5no2/html/v05i2a09p_0001.htm |publisher=[[Central Intelligence Agency]] |access-date=14 June 2012 |url-status= dead |archive-url= https://web.archive.org/web/20120927173306/https://www.cia.gov/library/center-for-the-study-of-intelligence/kent-csi/vol5no2/html/v05i2a09p_0001.htm |archive-date=27 September 2012 }}</ref> In 2009, the [[Czechoslovakia|Czechoslovak]] [[StB|state security secret police]] were proven to have used scopolamine at least three times to obtain confessions from alleged [[Enemy of the state|antistate]] [[dissident]]s.<ref>{{cite news | vauthors = Gazdík J, Navara L |title = Svědek: Grebeníček vězně nejen mlátil, ale dával jim i drogy |trans-title=A witness: Grebeníček not only beat prisoners, he also administered drugs to them |language = cs |publisher = [[Mladá fronta DNES|iDnes]] |date = 8 August 2009 |url = http://zpravy.idnes.cz/svedek-grebenicek-vezne-nejen-mlatil-ale-daval-jim-i-drogy-pmd-/domaci.asp?c=A090807_205833_domaci_vel |access-date = 10 August 2009 |url-status = live |archive-url = https://web.archive.org/web/20090811062349/http://zpravy.idnes.cz/svedek-grebenicek-vezne-nejen-mlatil-ale-daval-jim-i-drogy-pmd-/domaci.asp?c=A090807_205833_domaci_vel |archive-date = 11 August 2009 }}</ref>

===Use in crime===

Scopolamine can render a victim unconscious for 24 hours or more. In large doses, it can cause respiratory failure and death. The most common seems to be recorded in [[Colombia]], where unofficial estimates put the number of annual scopolamine incidents at approximately 50,000. A travel advisory published by the [[Bureau of Diplomatic Security|U.S. Overseas Security Advisory Council (OSAC)]] in 2012 stated: {{blockquote|One common and particularly dangerous method that criminals use in order to rob a victim is through the use of drugs. Scopolamine is most often administered in liquid or powder form in foods and beverages. The majority of these incidents occur in night clubs and bars, and usually men, perceived to be wealthy, are targeted by young, attractive women. It is recommended that, to avoid becoming a victim of scopolamine, a person should never accept food or beverages offered by strangers or new acquaintances, nor leave food or beverages unattended in their presence. Victims of scopolamine or other drugs should seek immediate medical attention.<ref>{{Cite web |url= https://www.osac.gov/Pages/ContentReportDetails.aspx?cid=12118 |title=Colombia 2012 Crime and Safety Report: Cartagena |date=4 March 2012 |publisher=[[Overseas Security Advisory Council]], [[United States Department of State]] |access-date=6 August 2015 |url-status= live |archive-url= https://web.archive.org/web/20130315175638/https://www.osac.gov/Pages/ContentReportDetails.aspx?cid=12118 |archive-date=15 March 2013 }}</ref>}}

Between 1998 and 2004, 13% of emergency-room admissions for "poisoning with criminal intentions" in a clinic of [[Bogotá]] have been attributed to scopolamine, and 44% to [[benzodiazepine]]s.<ref name= "Uribe_et_al_2005"/> Most commonly, the person has been poisoned by a robber who gave the victim a scopolamine-laced beverage, in the hope that the victim would become unconscious or unable to effectively resist the robbery.<ref name= "Uribe_et_al_2005"/>

Beside robberies, it is also allegedly involved in [[express kidnapping]]s and [[sexual assault]].<ref name="dom">{{cite news | vauthors = Domínguez I |title= Burundanga: the stealth drug that cancels the victim's willpower |url= http://elpais.com/elpais/2016/07/25/inenglish/1469445136_776085.html?id_externo_promo=ob-externo-english |date=25 July 2016 |access-date=12 August 2016 |work=Crime |agency=El País, Madrid |url-status=live |archive-url= https://web.archive.org/web/20160820222322/http://elpais.com/elpais/2016/07/25/inenglish/1469445136_776085.html?id_externo_promo=ob-externo-english |archive-date=20 August 2016 }}</ref> In 2008, the Hospital Clínic in [[Barcelona]] introduced a [[Medical guideline|protocol]] to help medical workers identify cases. In February 2015, Madrid hospitals adopted a similar working document.<ref name="dom"/> Hospital Clínic has found little scientific evidence to support this use and relies on the victims' stories to reach any conclusion.<ref name="dom"/> Although poisoning by scopolamine appears quite often in the media as an aid for raping, kidnapping, killing, or robbery, the effects of this drug and the way it is applied by criminals (transdermal injection, on playing cards and papers, etc.) are often exaggerated,<ref>{{Cite web |url=http://www.hoax-slayer.com/burundanga-warning.shtml |title= Burundanga Business Card Drug Warning | website= Hoax-Slayer.com |date= 12 October 2008|url-status= live| archive-url= https://web.archive.org/web/20090307163535/http://www.hoax-slayer.com/burundanga-warning.shtml| archive-date=7 March 2009}}</ref><ref>{{Cite news| url= http://urbanlegends.about.com/od/crime/a/burundanga.htm| title=Beware the Burundanga Man! |work= About.com Entertainment|access-date=19 December 2016| url-status= live| archive-url= https://web.archive.org/web/20170110140952/http://urbanlegends.about.com/od/crime/a/burundanga.htm|archive-date=10 January 2017}}</ref><ref>{{Cite news| url= http://www.snopes.com/crime/warnings/burundanga.asp |title= Burundanga/Scopolamine Warning| vauthors = Mikkelson D |work= snopes.com |access-date=19 December 2016}}</ref> especially skin exposure, as the dose that can be absorbed by the skin is too low to have any effect.<ref name= "dom" /> Scopolamine transdermal patches must be used for hours to days.<ref name= "White" />

There are certain other aspects of the usage of scopolamine in crimes. Powdered scopolamine is referred to as "devil's breath". In popular media and television, it is portrayed as a method to [[brainwashing|brainwash]] or control people into being defrauded by their attackers.<ref name="Case" >{{cite journal | vauthors = Reichert S, Lin C, Ong W, Him CC, Hameed S | title = Million dollar ride: Crime committed during involuntary scopolamine intoxication | journal = Canadian Family Physician | volume = 63 | issue = 5 | pages = 369–370 | date = May 2017 | pmid = 28500194 | pmc = 5429053 | url = https://www.cfp.ca/content/cfp/63/5/369.full.pdf | url-status = live | archive-date = 22 April 2021 | archive-url = https://web.archive.org/web/20210422180516/https://www.cfp.ca/content/cfp/63/5/369.full.pdf }}</ref><ref>{{cite web |title=World's Scariest Drug (Documentary Exclusive) | website=[[YouTube]] |url=https://www.youtube.com/watch?v=ToQ8PWYnu04 |language=en}}</ref><ref>{{cite web |title=أخطر مخدر في العالم (عدنا إلى كولومبيا) | website=[[YouTube]] |url=https://www.youtube.com/watch?v=iuPnouyasN4 |language=ar}}</ref><ref>{{cite web |title=المخدر الأخطر في العالم ستتعرض له بدون أن تشعر في أمريكا اللاتينية | website=[[YouTube]] |url=https://www.youtube.com/watch?v=wh8RVl6uA4I&t=97s |language=ar}}</ref> There is debate whether these claims are true.<ref>{{cite web | vauthors = Anderson L |title=Devil's Breath: Urban Legend or the World's Most Scary Drug? |url= https://www.drugs.com/illicit/devils-breath.html |website=Drugs.com |access-date=9 July 2019}}</ref><ref>{{cite news |date=2 September 2015 |title='Devil's breath' aka scopolamine: can it really zombify you? |work=The Guardian |url=https://www.theguardian.com/society/shortcuts/2015/sep/02/devils-breath-aka-scopolamine-can-it-really-zombify-you |access-date=4 January 2019 |vauthors=Saner E}}</ref> It is not verified if the powdered form is capable of inducing a suggestive state. The danger is real enough that in addition to the Overseas Security Advisory Council (OSAC) in 2012, the US Department of State, as well as the Government of Canada, published<ref>{{cite web |title=Colombia Travel Advisory |url=https://travel.state.gov/content/travel/en/traveladvisories/traveladvisories/colombia-travel-advisory.html |website=travel.state.gov |archive-url=https://web.archive.org/web/20220405083739/https://travel.state.gov/content/travel/en/traveladvisories/traveladvisories/colombia-travel-advisory.html |archive-date=5 April 2022 |url-status=live}}</ref><ref>{{cite web | author = Global Affairs Canada |title=Travel Advice and Advisories for Colombia |url=https://travel.gc.ca/destinations/colombia |website=Travel.gc.ca |archive-url=https://web.archive.org/web/20220516120636/https://travel.gc.ca/destinations/colombia |archive-date=16 May 2022 |date=16 November 2012 |url-status=live}}</ref> travel advisories warning travelers about the possibility of targeting.

Criminals using Devil's Breath often use attractive, young women, including women in dating apps<ref>{{cite web | url=https://www.semana.com/amp/salud/articulo/escopolamina-la-droga-borra-recuerdos-que-acecha-a-los-extranjeros-en-colombia-estos-son-sus-mortales-efectos/202423/ | title=Escopolamina, la droga "borra recuerdos" que acecha a los extranjeros en Colombia; estos son sus mortales efectos | date=23 January 2024 }}</ref> to target men that they believe are wealthy.<ref>{{cite web |title=Devil's Breath: Why Scopolamine Abuse is So Terrifying |url=https://www.northpointwashington.com/blog/devils-breath-scopolamine-abuse-terrifying/ |website=Northpoint Washington |date=9 May 2019}}</ref> The drug is known to produce [[anterograde amnesia|loss of memory following exposure]] and [[somnolence|sleepiness]], similar to the effect of [[benzodiazepines]] or [[alcohol poisoning]].<ref name="urlAtypical Drugs of Abuse">{{cite web | url = http://studentdoctor.net/2008/07/atypical-drugs-of-abuse/ | title = Atypical Drugs of Abuse | vauthors = Forest E | date = 27 July 2008 | work = Articles & Interviews | publisher = Student Doctor Network | url-status = live | archive-url = https://web.archive.org/web/20130527231559/http://studentdoctor.net/2008/07/atypical-drugs-of-abuse/ | archive-date = 27 May 2013 }}</ref><ref name="Differentiating the effects of cent">{{cite journal | vauthors = Curran HV, Pooviboonsuk P, Dalton JA, Lader MH | title = Differentiating the effects of centrally acting drugs on arousal and memory: an event-related potential study of scopolamine, lorazepam and diphenhydramine | journal = Psychopharmacology | volume = 135 | issue = 1 | pages = 27–36 | date = January 1998 | pmid = 9489931 | doi = 10.1007/s002130050482 | s2cid = 9872819 }}</ref>

== Research ==

Scopolamine is used as a research tool to study memory encoding. Initially, in human trials, relatively low doses of the muscarinic receptor antagonist scopolamine were found to induce temporary cognitive defects.<ref>{{cite journal | vauthors = Drachman DA, Leavitt J | title = Human memory and the cholinergic system. A relationship to aging? | journal = Archives of Neurology | volume = 30 | issue = 2 | pages = 113–121 | date = February 1974 | pmid = 4359364 | doi = 10.1001/archneur.1974.00490320001001 }}</ref> Since then, scopolamine has become a standard drug for experimentally inducing cognitive defects in animals.<ref name = "Hasselmo_1997">{{cite journal | vauthors = Hasselmo ME, Wyble BP | title = Free recall and recognition in a network model of the hippocampus: simulating effects of scopolamine on human memory function | journal = Behavioural Brain Research | volume = 89 | issue = 1–2 | pages = 1–34 | date = December 1997 | pmid = 9475612 | doi = 10.1016/s0166-4328(97)00048-x | s2cid = 584350 }}</ref><ref name = "More_2016">{{cite journal | vauthors = More SV, Kumar H, Cho DY, Yun YS, Choi DK | title = Toxin-Induced Experimental Models of Learning and Memory Impairment | journal = International Journal of Molecular Sciences | volume = 17 | issue = 9 | pages = 1447 | date = September 2016 | pmid = 27598124 | pmc = 5037726 | doi = 10.3390/ijms17091447 | doi-access = free }}</ref> Results in primates suggest that [[acetylcholine]] is involved in the encoding of new information into long-term memory.<ref>{{cite journal | vauthors = Ridley RM, Bowes PM, Baker HF, Crow TJ | title = An involvement of acetylcholine in object discrimination learning and memory in the marmoset | journal = Neuropsychologia | volume = 22 | issue = 3 | pages = 253–263 | year = 1984 | pmid = 6431311 | doi = 10.1016/0028-3932(84)90073-3 | s2cid = 7110504 }}</ref> Scopolamine has been shown to exert a greater impairment on [[episodic memory]], [[event-related potential]]s, [[memory retention]] and [[free recall]] compared to [[Diphenhydramine|DPH]] (an anticholinergic and [[antihistamine]]).<ref name="Differentiating the effects of cent"/>

Scopolamine produces detrimental effects on short-term memory, memory acquisition, learning, visual recognition memory, [[Visuospatial function|visuospatial]] praxis, visuospatial memory, visuoperceptual function, [[verbal recall]], and psychomotor speed.<ref>{{cite journal | vauthors = Flicker C, Serby M, Ferris SH | title = Scopolamine effects on memory, language, visuospatial praxis and psychomotor speed | journal = Psychopharmacology | volume = 100 | issue = 2 | pages = 243–250 | date = February 1990 | pmid = 2305013 | doi = 10.1007/bf02244414 | s2cid = 24645744 }}</ref><ref name = "Hasselmo_1997" /><ref name = "More_2016" /> It does not seem to impair recognition and memory retrieval, though.<ref name = "More_2016" /> Acetylcholine projections in hippocampal neurons, which are vital in mediating long-term potentiation, are inhibited by scopolamine.<ref name = "More_2016" /><ref>{{cite journal | vauthors = Lisboa SF, Vila-Verde C, Rosa J, Uliana DL, Stern CA, Bertoglio LJ, Resstel LB, Guimaraes FS | title = Tempering aversive/traumatic memories with cannabinoids: a review of evidence from animal and human studies | journal = Psychopharmacology | volume = 236 | issue = 1 | pages = 201–226 | date = January 2019 | pmid = 30604182 | doi = 10.1007/s00213-018-5127-x | s2cid = 58655082 }}</ref> Scopolamine inhibits cholinergic-mediated glutamate release in hippocampal neurons, which assist in depolarization, potentiation of action potential, and synaptic suppression. Scopolamine's effects on acetylcholine and glutamate release in the hippocampus favor retrieval-dominant cognitive functioning.<ref name = "More_2016" /> Scopolamine has been used to model the defects in cholinergic function for models of [[Alzheimer's]], dementia, [[fragile X syndrome]], and Down syndrome.<ref name = "More_2016" /><ref>{{cite journal | vauthors = Qin M, Zeidler Z, Moulton K, Krych L, Xia Z, Smith CB | title = Endocannabinoid-mediated improvement on a test of aversive memory in a mouse model of fragile X syndrome | journal = Behavioural Brain Research | volume = 291 | pages = 164–171 | date = September 2015 | pmid = 25979787 | pmc = 5003021 | doi = 10.1016/j.bbr.2015.05.003 }}</ref><ref>{{cite book | vauthors = Lott IT | title = Down Syndrome: From Understanding the Neurobiology to Therapy | chapter = Neurological phenotypes for Down syndrome across the life span | series = Progress in Brain Research | volume = 197 | pages = 101–21 | date = 2012 | pmid = 22541290 | doi = 10.1016/b978-0-444-54299-1.00006-6 | pmc=3417824| isbn = 978-0-444-54299-1 }}</ref><ref>{{cite journal | vauthors = Lagalwar S, Bordayo EZ, Hoffmann KL, Fawcett JR, Frey WH | title = Anandamides inhibit binding to the muscarinic acetylcholine receptor | journal = Journal of Molecular Neuroscience | volume = 13 | issue = 1–2 | pages = 55–61 | date = 1999 | pmid = 10691292 | doi = 10.1385/jmn:13:1-2:55 | s2cid = 22731716 }}</ref>

Scopolamine has been identified as a [[psychoplastogen]], which refers to a compound capable of promoting rapid and sustained [[neuroplasticity]] in a single dose.<ref>{{cite journal | vauthors = Olson DE | title = Psychoplastogens: A Promising Class of Plasticity-Promoting Neurotherapeutics | journal = Journal of Experimental Neuroscience | volume = 12 | pages = 1179069518800508 | date = September 19, 2018 | pmid = 30262987 | doi = 10.1177/1179069518800508 | pmc = 6149016 | s2cid = 52877093 }}</ref> It has been, and continues to be investigated as a rapid-onset [[antidepressant]], with a number of small studies finding positive results, particularly in female subjects.<ref>{{cite journal | vauthors = Drevets WC, Zarate CA, Furey ML | title = Antidepressant effects of the muscarinic cholinergic receptor antagonist scopolamine: a review | journal = Biological Psychiatry | volume = 73 | issue = 12 | pages = 1156–1163 | date = June 2013 | pmid = 23200525 | pmc = 4131859 | doi = 10.1016/j.biopsych.2012.09.031 }}</ref><ref>{{cite journal | vauthors = Hasselmann H | title = Scopolamine and depression: a role for muscarinic antagonism? | journal = CNS & Neurological Disorders Drug Targets | volume = 13 | issue = 4 | pages = 673–683 | date = 2014 | pmid = 24938776 | doi = 10.2174/1871527313666140618105710 }}</ref><ref>{{cite journal | vauthors = Jaffe RJ, Novakovic V, Peselow ED | title = Scopolamine as an antidepressant: a systematic review | journal = Clinical Neuropharmacology | volume = 36 | issue = 1 | pages = 24–26 | date = 2013 | pmid = 23334071 | doi = 10.1097/wnf.0b013e318278b703 | s2cid = 19740245 }}</ref><ref name="pmid27270172">{{cite journal | vauthors = Wohleb ES, Wu M, Gerhard DM, Taylor SR, Picciotto MR, Alreja M, Duman RS | title = GABA interneurons mediate the rapid antidepressant-like effects of scopolamine | journal = The Journal of Clinical Investigation | volume = 126 | issue = 7 | pages = 2482–2494 | date = July 2016 | pmid = 27270172 | pmc = 4922686 | doi = 10.1172/JCI85033 }}</ref>

[[NASA]] agreed to develop a nasal administration method. With a precise dosage, the NASA spray formulation has been shown to work faster and more reliably than the oral form to treat motion sickness.<ref>{{cite press release | title=NASA Signs Agreement to Develop Nasal Spray for Motion Sickness | website=NASA | date=12 October 2012 | url=http://spaceref.com/news/viewpr.html?pid=38893 | access-date=3 February 2022 }}{{Dead link|date=December 2023 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>

Although a fair amount of research has been applied to scopolamine in the field of medicine, its [[hallucinogenic]] (psychoactive) effects as well as the psychoactive effects of other antimuscarinic [[deliriants]] haven't been extensively researched or as well understood compared to other types of hallucinogens such as [[psychedelic drugs|psychedelic]] and [[Dissociatives|dissociative]] compounds, despite the alkaloid's long history of usage in mind-altering plant preparations.<ref name="pubmed.ncbi.nlm.nih.gov">{{cite journal | vauthors = Volgin AD, Yakovlev OA, Demin KA, Alekseeva PA, Kyzar EJ, Collins C, Nichols DE, Kalueff AV | title = Understanding Central Nervous System Effects of Deliriant Hallucinogenic Drugs through Experimental Animal Models | journal = ACS Chemical Neuroscience | volume = 10 | issue = 1 | pages = 143–154 | date = January 2019 | pmid = 30252437 | doi = 10.1021/acschemneuro.8b00433 | s2cid = 52824516 }}</ref>

== References ==

{{Reflist}}

== External links ==

* {{Commons category-inline|Scopolamine}}

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[[Category:Carboxylate esters]]

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