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

{{Distinguish||text=[[hyoscine]], another name for the drug scopolamine}}{{Short description|Tropane alkaloid}}

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| KEGG = D00147

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| IUPAC_name = (8-methyl-8-azabicyclo[3.2.1]-3-yl 3-hydroxy-2-phenylpropanoate

'''Hyoscyamine''' (also known as '''daturine''' or '''duboisine''') is a naturally occurring [[tropane alkaloid]] and plant toxin. It is a [[secondary metabolite]] found in certain plants of the family [[Solanaceae]], including [[Hyoscyamus niger|henbane]], [[Mandragora officinarum|mandrake]], [[Brugmansia|angel's trumpets]], [[Datura stramonium|jimsonweed]], [[Latua pubiflora|the sorcerers' tree]], and [[Atropa belladonna]] (deadly nightshade). It is the [[levorotary]] [[isomer]] of [[atropine]] (third of the three major nightshade alkaloids) and thus sometimes known as levo-atropine.<ref>{{cite journal | vauthors = Ushimaru R, Ruszczycky MW, Liu HW | title = Changes in Regioselectivity of H Atom Abstraction during the Hydroxylation and Cyclization Reactions Catalyzed by Hyoscyamine 6β-Hydroxylase | journal = Journal of the American Chemical Society | volume = 141 | issue = 2 | pages = 1062–1066 | date = January 2019 | pmid = 30545219 | pmc = 6488026 | doi = 10.1021/jacs.8b11585 }}</ref>

In 2021, it was the 272nd most commonly prescribed medication in the United States, with more than 900,000 prescriptions.<ref>{{cite web | title=The Top 300 of 2021 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=14 January 2024 | archive-date=15 January 2024 | archive-url=https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Hyoscyamine - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Hyoscyamine | access-date = 14 January 2024}}</ref>

==Medical uses==

Hyoscyamine is used to provide symptomatic relief of spasms caused by various lower abdominal and bladder disorders including [[peptic ulcer]]s, [[irritable bowel syndrome]], [[diverticulitis]], [[pancreatitis]], [[colic]], and [[interstitial cystitis]].<ref>{{Cite book | author = National Clinical Guideline Centre (UK) |url=https://www.ncbi.nlm.nih.gov/books/NBK132836/ |title=Treatment to improve bladder storage |publisher=[[Royal College of Physicians]] |year=2012 |edition=8th |series=NBK132836 |location= United Kingdom |pages=83 |language=en |via=[[National Library of Medicine]]}}</ref><ref name=":0">{{Cite web |title=Hyoscyamine Uses, Side Effects & Warnings |url=https://www.drugs.com/mtm/hyoscyamine.html |url-status=live |archive-url=https://web.archive.org/web/20220820204721/https://www.drugs.com/mtm/hyoscyamine.html |archive-date=20 August 2022 |access-date=20 August 2022 |website=[[Drugs.com]] |language=en}}</ref><ref>{{Cite web |title=Bladder Control Medicines {{!}} NIDDK |url=https://www.niddk.nih.gov/health-information/urologic-diseases/bladder-control-medicines |url-status=live |archive-url=https://web.archive.org/web/20220820204616/https://www.niddk.nih.gov/health-information/urologic-diseases/bladder-control-medicines |archive-date=20 August 2022 |access-date=20 August 2022 |website=[[National Institute of Diabetes and Digestive and Kidney Diseases]] |language=en-US}}</ref> It has also been used to relieve some heart problems, control some of the symptoms of [[Parkinson's disease]], as well as for control of abnormal respiratory symptoms and "hyper-mucus secretions" in patients with lung disease.<ref>{{Cite web |title=Hyoscyamine: MedlinePlus Drug Information |url=https://medlineplus.gov/druginfo/meds/a684010.html |url-status=live |archive-url=https://web.archive.org/web/20220820211337/https://medlineplus.gov/druginfo/meds/a684010.html |archive-date=20 August 2022 |access-date=20 August 2022 |website=[[MedlinePlus|medlineplus.gov]] |language=en}}</ref>

[[File:Clap Mixture, Pharmacy Museum, New Orleans, LA.jpg|thumb|alt=Brown glass medicine bottle with label reading, "CLAP MIXTURE," a list of ingredients, "CAUTION -- It is dangerous to exceed the stated dose / DOSES / 1/2 fluid ounce three times a day, in water / SHAKE THE BOTTLE"|The ingredients of this [[Gonorrhea|Clap]] Mixture are sodium citrate, sodium bicarbonate, liquid extract of hyoscyamine and chloroform dissolved in water.]]

It is also useful in pain control for neuropathic pain, chronic pain and palliative care — "comfort care" — for those with intractable pain from treatment resistant, untreatable, and incurable diseases. When combined with opioids it increases the level of analgesia (pain relief) obtained.<ref>{{cite journal | vauthors = Harden RN | title = Chronic neuropathic pain. Mechanisms, diagnosis, and treatment | journal = The Neurologist | volume = 11 | issue = 2 | pages = 111–122 | date = March 2005 | pmid = 15733333 | doi = 10.1097/01.nrl.0000155180.60057.8e | s2cid = 12602416 }}</ref> Several mechanisms are thought to contribute to this effect. The closely related drugs atropine and [[hyoscine]] and other members of the anticholinergic drug group like [[cyclobenzaprine]], [[trihexyphenidyl]], and [[orphenadrine]] are also used for this purpose.<ref>{{cite journal | vauthors = Ali-Melkkilä T, Kanto J, Iisalo E | title = Pharmacokinetics and related pharmacodynamics of anticholinergic drugs | journal = Acta Anaesthesiologica Scandinavica | volume = 37 | issue = 7 | pages = 633–642 | date = October 1993 | pmid = 8249551 | doi = 10.1111/j.1399-6576.1993.tb03780.x | s2cid = 22808654 }}</ref> When hyoscyamine is used along with opioids or other anti-peristaltic agents, measures to prevent constipation are especially important given the risk of paralytic [[ileus]].<ref name="Kamimura_2020">{{cite journal | vauthors = Kamimura A, Howard S, Weaver S, Panahi S, Ashby J | title = The Use of Complementary and Alternative Medicine Strategies, Opioids, and Nonsteroidal Anti-Inflammatory Drugs (NSAIDS) Among Patients Attending a Free Clinic | journal = Journal of Patient Experience | volume = 7 | issue = 6 | pages = 1701–1707 | date = December 2020 | pmid = 33457633 | pmc = 7786764 | doi = 10.1177/2374373520937514 }}</ref>

==Adverse effects==

Side effects include dry mouth and throat, increased appetite leading to weight gain, eye pain, blurred vision, restlessness, dizziness, [[Heart arrhythmia|arrhythmia]], flushing, and faintness.<ref name=":0" /> An overdose will cause headache, nausea, vomiting, and central nervous system symptoms including disorientation, hallucinations, euphoria, sexual arousal, short-term memory loss, and possible coma in extreme cases. The euphoric and sexual effects are stronger than those of atropine but weaker than those of [[hyoscine]], as well as [[dicycloverine]], [[orphenadrine]], [[cyclobenzaprine]], [[trihexyphenidyl]], and ethanolamine antihistamines like [[phenyltoloxamine]].<ref>{{cite book | vauthors = Kang M, Galuska MA, Ghassemzadeh S | chapter = Benzodiazepine Toxicity |date=2022 | chapter-url=http://www.ncbi.nlm.nih.gov/books/NBK482238/ | title = StatPearls |archive-url= https://web.archive.org/web/20220820213407/https://www.ncbi.nlm.nih.gov/books/NBK482238/ |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=29489152 | archive-date=20 August 2022 }}</ref><ref>{{Cite web |title=Hyoscyamine Sulfate Sublingual Tablets, 0.125 mgRx Only |url=https://www.dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=ec5a3a71-54b7-428f-9017-51848a588c97 |url-status=live |archive-url=https://web.archive.org/web/20220820213627/https://www.dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=ec5a3a71-54b7-428f-9017-51848a588c97 |archive-date=20 August 2022 |access-date=20 August 2022 |website=www.dailymed.nlm.nih.gov}}</ref>

==Pharmacology==

Hyoscyamine is an [[antimuscarinic]]; i.e., an antagonist of [[muscarinic acetylcholine receptor]]s. It blocks the action of [[acetylcholine]] at sweat glands (sympathetic) and at [[parasympathetic]] sites in salivary glands, stomach secretions, heart muscle, [[sinoatrial node]], smooth muscle in the [[Human gastrointestinal tract|gastrointestinal tract]], and the [[central nervous system]]. It increases cardiac output and heart rate, lowers blood pressure and dries secretions.<ref name="nhl-hyo">{{cite web | author1 = Edwards Pharmaceuticals, Inc. | author2 = Belcher Pharmaceuticals, Inc. | title = DailyMed | publisher = U.S. National Library of Medicine | date = May 2010 | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=f33a4774-9fbb-4782-a7e1-068e83b7504d | access-date = 13 January 2013}}</ref> It may antagonize [[serotonin]].<ref name="kapoor">{{cite book | vauthors = Kapoor AK, Raju SM |year=2013 |title= Illustrated Medical Pharmacology |page=131|url=https://books.google.com/books?id=Le28AQAAQBAJ&q=Hyoscyamine+serotonin&pg=PA131 |publisher=JP Medical Ltd |isbn=9789350906552 |access-date= 11 January 2014}}</ref> At comparable doses, hyoscyamine has 98 percent of the [[anticholinergic]] power of atropine. The other major [[Atropa belladonna]]-derived drug [[hyoscine]] (known in the United States as Scopolamine) has 92 per cent of the antimuscarinic potency of atropine.<ref name="kapoor" />

==Biosynthesis in plants==

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

Hyoscyamine can be extracted from plants of the family [[Solanaceae]], notably ''[[Datura stramonium]]''. As hyoscyamine is a direct [[precursor (chemistry)|precursor]] in the [[Hyoscine#Biosynthesis in plants|plant biosynthesis of hyoscine]], it is produced via the same [[metabolic pathway]].<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>

The [[biosynthesis]] of hyoscine begins with the [[decarboxylation]] of ''L''-[[ornithine]] to [[putrescine]] by [[ornithine decarboxylase]] ([http://enzyme.expasy.org/EC/4.1.1.17 EC 4.1.1.17]). Putrescine is [[Methylation|methylated]] to ''N''-methylputrescine by [[putrescine N-methyltransferase|putrescine ''N''-methyltransferase]] ([http://enzyme.expasy.org/EC/2.1.1.53 EC 2.1.1.53]).<ref name="Ziegler2008"/>

A [[putrescine oxidase]] ([http://enzyme.expasy.org/EC/1.4.3.10 EC 1.4.3.10]) that specifically recognizes methylated putrescine catalyzes the [[deamination]] of this compound to 4-methylaminobutanal which then undergoes a spontaneous ring formation to ''N''-methylpyrrolium cation. In the next step, the pyrrolium cation condenses with [[acetoacetic acid]] yielding [[hygrine]]. No enzymatic activity could be demonstrated that catalyzes this reaction. Hygrine further rearranges to [[tropinone]].<ref name="Ziegler2008" />

Subsequently, [[tropinone reductase I]] ([http://enzyme.expasy.org/EC/1.1.1.206 EC 1.1.1.206]) 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]].

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

==Bush medicine basis==

A [[bush medicine]] developed by [[Aboriginal Australians|Aboriginal peoples]] of the [[eastern states of Australia]] from the soft [[corkwood]] tree, or ''[[Duboisia myoporoides]]'', was used by the [[Allies of World War II|Allies]] in World War II to stop soldiers getting [[Seasickness|seasick]] when they sailed across the [[English Channel]] during the [[Invasion of Normandy]]. Later, it was found that the same substance could be used in the production of [[scopolamine]] and hyoscyamine, which are used in [[eye surgery]], and a multi-million 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>

== Society and culture ==

=== Brand names ===

Brand names for hyoscyamine include Symax, HyoMax, Anaspaz, Egazil, Buwecon, Cystospaz, Levsin, Levbid, Levsinex, Donnamar, NuLev, Spacol T/S, and Neoquess.<ref>{{Cite web |title=Hyoscyamine - brand name list from Drugs.com |url=https://www.drugs.com/ingredient/hyoscyamine.html |url-status=live |archive-url=https://web.archive.org/web/20220820211121/https://www.drugs.com/ingredient/hyoscyamine.html |archive-date=20 August 2022 |access-date=20 August 2022 |website=[[Drugs.com]] |language=en}}</ref>

== References ==

{{Reflist}}

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{{Drugs for functional gastrointestinal disorders}}

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[[Category:Tropane alkaloids]]

[[Category:Muscarinic antagonists]]

[[Category:Antispasmodics]]

[[Category:Oneirogens]]

[[Category:Tropane alkaloids found in Solanaceae]]

[[Category:Carboxylate esters]]

[[Category:Entheogens]]

[[Category:Plant toxins]]