Hyoscyamine

Last updated

Hyoscyamine
Hyoscyamine.svg
Hyoscyamine-from-xtal-3D-balls.png
Clinical data
Trade names Anaspaz, Levbid, Levsin
AHFS/Drugs.com Monograph
MedlinePlus a684010
Routes of
administration
By mouth, Injection
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 50% protein binding
Metabolism Liver
Elimination half-life 3–5 hrs.
Excretion Kidney
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 InfoCard 100.002.667 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C17H23NO3
Molar mass 289.375 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 Yes check.svgY
  • Key:RKUNBYITZUJHSG-FXUDXRNXSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (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]

Contents

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

Medical uses

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]

The ingredients of this Clap Mixture are sodium citrate, sodium bicarbonate, liquid extract of hyoscyamine and chloroform dissolved in water. Clap Mixture, Pharmacy Museum, New Orleans, LA.jpg
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

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

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

Biochemistry of tropane class compounds. Hyoscyamine and scopolamine are present and labeled in the diagram. Tropane alkaloids biochemistry.png
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.

Scopolamine biosynthesis.svg

Bush medicine basis

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

Brand names

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

Related Research Articles

<span class="mw-page-title-main">Scopolamine</span> Tropane alkaloid & anticholinergic drug

Scopolamine, also known as hyoscine, or Devil's Breath, is a natural or synthetically produced tropane alkaloid and anticholinergic drug that is used as a medication to treat motion sickness and postoperative nausea and vomiting. It is also sometimes used before surgery to decrease saliva. When used by injection, effects begin after about 20 minutes and last for up to 8 hours. It may also be used orally and as a transdermal patch since it has been long known to have transdermal bioavailability.

<span class="mw-page-title-main">Atropine</span> Anticholinergic medication used as antidote for nerve agent poisoning

Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically given intravenously or by injection into a muscle. Eye drops are also available which are used to treat uveitis and early amblyopia. The intravenous solution usually begins working within a minute and lasts half an hour to an hour. Large doses may be required to treat some poisonings.

<i>Atropa belladonna</i> Species of toxic flowering plant in the nightshade family.

Atropa belladonna, commonly known as belladonna or deadly nightshade, is a toxic perennial herbaceous plant in the nightshade family Solanaceae, which also includes tomatoes, potatoes and aubergine (eggplant). It is native to Europe and Western Asia, including Turkey. Its distribution extends from Ireland in the west to western Ukraine and the Iranian province of Gilan in the east. It is also naturalised or introduced in some parts of Canada, North Africa and the United States.

An antispasmodic is a pharmaceutical drug or other agent that suppresses muscle spasms.

Anticholinergics are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central and peripheral nervous system.

<span class="mw-page-title-main">Ipratropium bromide</span> Type of anticholinergic

Ipratropium bromide, sold under the trade name Atrovent among others, is a type of anticholinergic medication which is applied by different routes: inhaler, nebulizer, or nasal spray, for different reasons.

<span class="mw-page-title-main">Phytochemistry</span> Study of phytochemicals, which are chemicals derived from plants

Phytochemistry is the study of phytochemicals, which are chemicals derived from plants. Phytochemists strive to describe the structures of the large number of secondary metabolites found in plants, the functions of these compounds in human and plant biology, and the biosynthesis of these compounds. Plants synthesize phytochemicals for many reasons, including to protect themselves against insect attacks and plant diseases. The compounds found in plants are of many kinds, but most can be grouped into four major biosynthetic classes: alkaloids, phenylpropanoids, polyketides, and terpenoids.

<span class="mw-page-title-main">Diphenoxylate</span> Centrally active opioid drug used for the treatment of diarrhea

Diphenoxylate is a centrally active opioid drug of the phenylpiperidine series that is used as a combination drug with atropine for the treatment of diarrhea. Diphenoxylate is an opioid and acts by slowing intestinal contractions; the atropine is present to prevent drug abuse and overdose. It should not be given to children due to the risk that they will stop breathing and should not be used in people with Clostridium difficile infection.

<span class="mw-page-title-main">Orphenadrine</span> Muscle relaxant drug

Orphenadrine is an anticholinergic drug of the ethanolamine antihistamine class; it is closely related to diphenhydramine. It is a muscle relaxant that is used to treat muscle pain and to help with motor control in Parkinson's disease, but has largely been superseded by newer drugs. It is considered a dirty drug due to its multiple mechanisms of action in different pathways. It was discovered and developed in the 1940s.

<span class="mw-page-title-main">Hyoscine butylbromide</span> Anticholinergic medication

Hyoscine butylbromide, also known as scopolamine butylbromide and sold under the brandname Buscopan among others, is an anticholinergic medication used to treat abdominal pain, esophageal spasms, bladder spasms, biliary colic, and renal colic. It is also used to improve excessive respiratory secretions at the end of life. Hyoscine butylbromide can be taken by mouth, injection into a muscle, or into a vein.

<span class="mw-page-title-main">Trihexyphenidyl</span> Antispasmodic drug

Trihexyphenidyl is an antispasmodic drug used to treat stiffness, tremors, spasms, and poor muscle control. It is an agent of the antimuscarinic class and is often used in management of Parkinson's disease. It was approved by the FDA for the treatment of Parkinson's in the US in 2003.

<span class="mw-page-title-main">Muscarinic antagonist</span> Drug that binds to but does not activate muscarinic cholinergic receptors

A muscarinic receptor antagonist (MRA), also called an antimuscarinic, is a type of anticholinergic agent that blocks the activity of the muscarinic acetylcholine receptor. The muscarinic receptor is a protein involved in the transmission of signals through certain parts of the nervous system, and muscarinic receptor antagonists work to prevent this transmission from occurring. Notably, muscarinic antagonists reduce the activation of the parasympathetic nervous system. The normal function of the parasympathetic system is often summarised as "rest-and-digest", and includes slowing of the heart, an increased rate of digestion, narrowing of the airways, promotion of urination, and sexual arousal. Muscarinic antagonists counter this parasympathetic "rest-and-digest" response, and also work elsewhere in both the central and peripheral nervous systems.

<span class="mw-page-title-main">Difenoxin</span> Chemical compound

Difenoxin is an opioid drug used, often in combination with atropine, to treat diarrhea. It is the principal metabolite of diphenoxylate.

<span class="mw-page-title-main">Tropane alkaloid</span> Class of chemical compounds

Tropane alkaloids are a class of bicyclic [3.2.1] alkaloids and secondary metabolites that contain a tropane ring in their chemical structure. Tropane alkaloids occur naturally in many members of the plant family Solanaceae. Certain tropane alkaloids such as cocaine and scopolamine are notorious for their psychoactive effects, related usage and cultural associations. Particular tropane alkaloids such as these have pharmacological properties and can act as anticholinergics or stimulants.

<span class="mw-page-title-main">Biosynthesis of cocaine</span>

The biosynthesis of cocaine has long attracted the attention of biochemists and organic chemists. This interest is partly motivated by the strong physiological effects of cocaine, but a further incentive was the unusual bicyclic structure of the molecule. The biosynthesis can be viewed as occurring in two phases, one phase leading to the N-methylpyrrolinium ring, which is preserved in the final product. The second phase incorporates a C4 unit with formation of the bicyclic tropane core.

<span class="mw-page-title-main">Tropic acid</span> Chemical compound

Tropic acid is a chemical with IUPAC name 3-hydroxy-2-phenylpropanoic acid and condensed structural formula HOCH2CHPhCOOH. It is a laboratory reagent used in the chemical synthesis of atropine and hyoscyamine. Tropic acid is a chiral substance, existing as either a racemic mixture or as a single enantiomer.

<i>Mandragora</i> (genus) Genus of plants

Mandragora is a plant genus belonging to the nightshade family (Solanaceae). Members of the genus are known as mandrakes. Between three and five species are placed in the genus. The one or two species found around the Mediterranean constitute the mandrake of ancient writers such as Dioscorides. Two or three further species are found eastwards into China. All are perennial herbaceous plants, with large tap roots and leaves in the form of a rosette. Individual flowers are bell-shaped, whitish through to violet, and followed by yellow or orange berries.

<span class="mw-page-title-main">Apoatropine</span> Chemical compound

Apoatropine (atropatropine) is a member of class of tropane alkaloids. Chemically, it is an ester formed from tropine and atropic acid. Apoatropine can be found in plants of family Solanaceae. It is a bitter crystalline alkaloid. Examples of related tropane alkaloids include atropine, hyoscyamine, and hyoscine. Though apoatropine is found in various plants, it can also be prepared by the dehydration of atropine using nitric acid. Apoatropine is used as a pigment.

<span class="mw-page-title-main">Cholinergic blocking drug</span> Drug that block acetylcholine in synapses of cholinergic nervous system

Cholinergic blocking drugs are a group of drugs that block the action of acetylcholine (ACh), a neurotransmitter, in synapses of the cholinergic nervous system. They block acetylcholine from binding to cholinergic receptors, namely the nicotinic and muscarinic receptors.

Bellergal is a combination of levorotatory alkaloids of belladonna, ergotamine tartrate, and phenobarbital, used for the treatment of functional menopause, such as hot flashes and night sweat.

References

  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. 1 2 "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. 1 2 Kapoor AK, Raju SM (2013). Illustrated Medical Pharmacology. JP Medical Ltd. p. 131. ISBN   9789350906552 . Retrieved 11 January 2014.
  15. 1 2 3 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.