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{{Distinguish||text=[[hyoscine]], another name for the drug scopolamine}}{{Short description|Tropane alkaloid}}
{{short description|Pharmaceutical drug}}
{{Use dmy dates|date=January 2024}}
⚫
{{Drugbox| Verifiedfields = changed
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
⚫
| Verifiedfields = changed
| Watchedfields =
| Watchedfields =
| verifiedrevid = 461742575
| verifiedrevid = 461742575
⚫
| IUPAC_name = (''S'')-(1''R'',3''r'',5''S'')-8-methyl-8-azabicyclo[3.2.1]octan-3-yl 3-hydroxy-2-phenylpropanoate
| image = Hyoscyamine.svg
| image = Hyoscyamine.svg
| width = 200px
| width = 200
| alt =
| image2 = Hyoscyamine-from-xtal-3D-balls.png
| image2 = Hyoscyamine-from-xtal-3D-balls.png
| alt2 =


<!--Clinical data-->
<!-- Clinical data -->
| tradename = Anaspaz, Levbid, Levsin
| tradename = Anaspaz, Levbid, Levsin
| Drugs.com = {{drugs.com|monograph|hyoscyamine}}
| Drugs.com = {{drugs.com|monograph|hyoscyamine}}
| MedlinePlus = a684010
| MedlinePlus = a684010
| pregnancy_category = C{{where|date=April 2015}}
| pregnancy_category =
⚫
| routes_of_administration = [[By mouth]], Injection
⚫
| ATC_prefix = A03
⚫
| ATC_suffix = BA03

| legal_AU = S4
| legal_AU = S4
| legal_US = Rx only
| legal_US = Rx only
⚫
| routes_of_administration = Oral, Injection


<!--Pharmaeecokinetic data-->
<!-- Pharmaeecokinetic data -->
| bioavailability = 50% protein binding
| bioavailability = 50% protein binding
| metabolism = Hepatic
| metabolism = [[Liver]]
| elimination_half-life = 3–5 hrs.
| elimination_half-life = 3–5 hrs.
| excretion = Urine
| excretion = [[Kidney]]


<!--Identifiers-->
<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 101-31-5
| CAS_number = 101-31-5
⚫
| ATC_prefix = A03
⚫
| ATC_suffix = BA03
| PubChem = 154417
| PubChem = 154417
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
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| UNII_Ref = {{fdacite|correct|FDA}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = PX44XO846X
| UNII = PX44XO846X
| KEGG = D00147
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 17486
| ChEBI = 17486
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| ChEMBL = 1697729
| ChEMBL = 1697729


<!--Chemical data-->
<!-- Chemical data -->
⚫
| IUPAC_name = (''S'')-(1''R'',3''r'',5''S'')-8-methyl-8-azabicyclo[3.2.1]octan-3-yl 3-hydroxy-2-phenylpropanoate
| C=17 | H=23 | N=1 | O=3
| C=17 | H=23 | N=1 | O=3
| smiles = CN3[C@H]1CC[C@@H]3C[C@@H](C1)OC(=O)[C@H](CO)c2ccccc2
| smiles = CN3[C@H]1CC[C@@H]3C[C@@H](C1)OC(=O)[C@H](CO)c2ccccc2
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}}
}}


'''Hyoscyamine''' (also known as '''daturine''') is a naturally occurring [[tropane alkaloid]] and plant toxin. It is a [[secondary metabolite]] found in certain plants of the family [[Solanaceae]], including henbane (''[[Hyoscyamus niger]]''), mandrake (''[[Mandragora officinarum]]''), angel's trumpets (''[[Brugmansia]]'' spp.), jimsonweed (''[[Datura stramonium]]''), tomato (''[[Solanum lycopersicum]]''), the sorcerers' tree (''[[Latua pubiflora]]''), and deadly nightshade (''[[Atropa belladonna]]''). It is the [[levorotary]] [[isomer]] of [[atropine]] (third of the three major nightshade alkaloids) and thus sometimes known as levo-atropine.
'''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>
Brand names for hyoscyamine include '''Symax''', '''HyoMax''', '''Anaspaz''', '''Egazil''', '''Buwecon''', '''Cystospaz''', '''Levsin''', '''Levbid''', '''Levsinex''', '''Donnamar''', '''NuLev''', '''Spacol T/S''', and '''Neoquess'''.


==Uses==
==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>
{{unreferenced section|date=May 2018}}
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]]. 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.


[[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. 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. 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]].

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==
==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>
{{unreferenced section|date=June 2019}}
⚫
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. 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]].


==Pharmacology==
==Pharmacology==
Hyoscyamine is an [[antimuscarinic]]; i.e., an antagonist of [[muscarinic acetylcholine receptor]]s. It blocks the action of [[acetylcholine]] at [[parasympathetic]] sites in sweat glands, 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">{{Citation
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" />
| last = Edwards Pharmaceuticals, Inc.
| author-link =
| last2 = Belcher Pharmaceuticals, Inc.
| author2-link =
| 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 = January 13, 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&pg=PA131&dq=Hyoscyamine+serotonin#v=onepage |publisher=JP Medical Ltd |isbn=9789350906552 |access-date= January 11, 2014}}</ref> At comparable doses, hyoscyamine has 98 per cent of the [[anticholinergic]] power of [[atropine]]. The other major [[Atropa belladonna|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==
==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 = 735–69 | year = 2008 | pmid = 18251710 | doi = 10.1146/annurev.arplant.59.032607.092730 }}</ref>
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"/>
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"/>
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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" />
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 = 513–20 | date = May 2006 | pmid = 16720272 | doi = 10.1016/j.chembiol.2006.03.005 | doi-access = free }}</ref> oxidizes and rearranges littorine to hyoscyamine [[aldehyde]].
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]]
[[File:Scopolamine biosynthesis.svg|center|800px]]
==Bush medicine basis==
==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]] on their way to liberate France and defeat [[Adolf Hitler|Hitler]] 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>
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 ==
== References ==
{{Reflist|2}}
{{Reflist}}


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{{Ancient anaesthesia-footer}}
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{{Hallucinogens}}
{{Hallucinogens}}
{{Muscarinic acetylcholine receptor modulators}}
{{Muscarinic acetylcholine receptor modulators}}
{{Portal bar | Medicine}}
{{Authority control}}


[[Category:Tropane alkaloids]]
[[Category:Tropane alkaloids]]
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[[Category:Oneirogens]]
[[Category:Oneirogens]]
[[Category:Tropane alkaloids found in Solanaceae]]
[[Category:Tropane alkaloids found in Solanaceae]]
[[Category:Propionates]]
[[Category:Carboxylate esters]]
[[Category:Entheogens]]
[[Category:Entheogens]]
[[Category:Alkaloids]]
[[Category:Plant toxins]]

Latest revision as of 20:13, 11 July 2024

Not to be confused with hyoscine, another name for the drug scopolamine.

Hyoscyamine
Clinical data
Trade namesAnaspaz, Levbid, Levsin
AHFS/Drugs.comMonograph
MedlinePlusa684010
Routes of
administration		By mouth, Injection
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability50% protein binding
MetabolismLiver
Elimination half-life3–5 hrs.
ExcretionKidney
Identifiers
  • (S)-(1R,3r,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl 3-hydroxy-2-phenylpropanoate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.002.667 Edit this at Wikidata
Chemical and physical data
FormulaC17H23NO3
Molar mass289.375 g·mol−1
3D model (JSmol)
  • CN3[C@H]1CC[C@@H]3C[C@@H](C1)OC(=O)[C@H](CO)c2ccccc2
  • InChI=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-/m1/s1 checkY
  • Key:RKUNBYITZUJHSG-FXUDXRNXSA-N checkY
 ☒NcheckY (what is this?)  (verify)

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 henbane, mandrake, angel's trumpets, jimsonweed, 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.[1]

In 2021, it was the 272nd most commonly prescribed medication in the United States, with more than 900,000 prescriptions.[2][3]

Medical uses

[edit]

Hyoscyamine is used to provide symptomatic relief of spasms caused by various lower abdominal and bladder disorders including peptic ulcers, irritable bowel syndrome, diverticulitis, pancreatitis, colic, and interstitial cystitis.[4][5][6] 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.[7]

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 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.[8] 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.[9] 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.[10]

Adverse effects

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Side effects include dry mouth and throat, increased appetite leading to weight gain, eye pain, blurred vision, restlessness, dizziness, arrhythmia, flushing, and faintness.[5] 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.[11][12]

Pharmacology

[edit]

Hyoscyamine is an antimuscarinic; i.e., an antagonist of muscarinic acetylcholine receptors. 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 gastrointestinal tract, and the central nervous system. It increases cardiac output and heart rate, lowers blood pressure and dries secretions.[13] It may antagonize serotonin.[14] 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.[14]

Biosynthesis in plants

[edit]
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 in the plant biosynthesis of hyoscine, it is produced via the same metabolic pathway.[15]

The biosynthesis of hyoscine begins with the decarboxylation of L-ornithine to putrescine by ornithine decarboxylase (EC 4.1.1.17). Putrescine is methylated to N-methylputrescine by putrescine N-methyltransferase (EC 2.1.1.53).[15]

A putrescine oxidase (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.[15]

Subsequently, tropinone reductase I (EC 1.1.1.206) converts tropinone to tropine which condenses with phenylalanine-derived phenyllactate to littorine. A cytochrome P450 classified as Cyp80F1[16] oxidizes and rearranges littorine to hyoscyamine aldehyde.

Bush medicine basis

[edit]

A bush medicine developed by Aboriginal peoples of the eastern states of Australia from the soft corkwood tree, or Duboisia myoporoides, was used by the Allies in World War II to stop soldiers getting 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.[17]

Society and culture

[edit]

Brand names

[edit]

Brand names for hyoscyamine include Symax, HyoMax, Anaspaz, Egazil, Buwecon, Cystospaz, Levsin, Levbid, Levsinex, Donnamar, NuLev, Spacol T/S, and Neoquess.[18]

References

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  1. ^ Ushimaru R, Ruszczycky MW, Liu HW (January 2019). "Changes in Regioselectivity of H Atom Abstraction during the Hydroxylation and Cyclization Reactions Catalyzed by Hyoscyamine 6β-Hydroxylase". Journal of the American Chemical Society. 141 (2): 1062–1066. doi:10.1021/jacs.8b11585. PMC 6488026. PMID 30545219.
  2. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  3. ^ "Hyoscyamine - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  4. ^ National Clinical Guideline Centre (UK) (2012). Treatment to improve bladder storage. NBK132836 (8th ed.). United Kingdom: Royal College of Physicians. p. 83 – via National Library of Medicine.
  5. ^ a b "Hyoscyamine Uses, Side Effects & Warnings". Drugs.com. Archived from the original on 20 August 2022. Retrieved 20 August 2022.
  6. ^ "Bladder Control Medicines | NIDDK". National Institute of Diabetes and Digestive and Kidney Diseases. Archived from the original on 20 August 2022. Retrieved 20 August 2022.
  7. ^ "Hyoscyamine: MedlinePlus Drug Information". medlineplus.gov. Archived from the original on 20 August 2022. Retrieved 20 August 2022.
  8. ^ Harden RN (March 2005). "Chronic neuropathic pain. Mechanisms, diagnosis, and treatment". The Neurologist. 11 (2): 111–122. doi:10.1097/01.nrl.0000155180.60057.8e. PMID 15733333. S2CID 12602416.
  9. ^ Ali-Melkkilä T, Kanto J, Iisalo E (October 1993). "Pharmacokinetics and related pharmacodynamics of anticholinergic drugs". Acta Anaesthesiologica Scandinavica. 37 (7): 633–642. doi:10.1111/j.1399-6576.1993.tb03780.x. PMID 8249551. S2CID 22808654.
  10. ^ Kamimura A, Howard S, Weaver S, Panahi S, Ashby J (December 2020). "The Use of Complementary and Alternative Medicine Strategies, Opioids, and Nonsteroidal Anti-Inflammatory Drugs (NSAIDS) Among Patients Attending a Free Clinic". Journal of Patient Experience. 7 (6): 1701–1707. doi:10.1177/2374373520937514. PMC 7786764. PMID 33457633.
  11. ^ Kang M, Galuska MA, Ghassemzadeh S (2022). "Benzodiazepine Toxicity". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 29489152. Archived from the original on 20 August 2022.
  12. ^ "Hyoscyamine Sulfate Sublingual Tablets, 0.125 mgRx Only". www.dailymed.nlm.nih.gov. Archived from the original on 20 August 2022. Retrieved 20 August 2022.
  13. ^ Edwards Pharmaceuticals, Inc., Belcher Pharmaceuticals, Inc. (May 2010). "DailyMed". U.S. National Library of Medicine. Retrieved 13 January 2013.
  14. ^ a b Kapoor AK, Raju SM (2013). Illustrated Medical Pharmacology. JP Medical Ltd. p. 131. ISBN 9789350906552. Retrieved 11 January 2014.
  15. ^ a b c Ziegler J, Facchini PJ (2008). "Alkaloid biosynthesis: metabolism and trafficking". Annual Review of Plant Biology. 59 (1): 735–769. doi:10.1146/annurev.arplant.59.032607.092730. PMID 18251710.
  16. ^ Li R, Reed DW, Liu E, Nowak J, Pelcher LE, Page JE, et al. (May 2006). "Functional genomic analysis of alkaloid biosynthesis in Hyoscyamus niger reveals a cytochrome P450 involved in littorine rearrangement". Chemistry & Biology. 13 (5): 513–520. doi:10.1016/j.chembiol.2006.03.005. PMID 16720272.
  17. ^ "Visitors to Art of Healing exhibition told how Australian Indigenous bush medicine was given to every allied soldier landing at Normandy on D-Day". King's College London. 7 June 2019. Retrieved 2 June 2020.
  18. ^ "Hyoscyamine - brand name list from Drugs.com". Drugs.com. Archived from the original on 20 August 2022. Retrieved 20 August 2022.
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