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,

tomato The tomato is the edible berry of the plant ''Solanum lycopersicum'', commonly known as the tomato plant. The species originated in western South America, Mexico, and Central America. The Mexican Nahuatl word gave rise to the Spanish word ...

, the sorcerers' tree, and deadly nightshade. It is the levorotary

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Is ...

atropine 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 ...

(third of the three major nightshade alkaloids) and thus sometimes known as levo-atropine. Brand names for hyoscyamine include Symax, HyoMax, Anaspaz, Egazil, Buwecon, Cystospaz, Levsin, Levbid, Levsinex, Donnamar, NuLev, Spacol T/S, and Neoquess.

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 Diverticulitis, specifically colonic diverticulitis, is a gastrointestinal disease characterized by inflammation of abnormal pouches— diverticula—which can develop in the wall of the large intestine. Symptoms typically include lower abdomi ...

pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic p ...

colic Colic or cholic () is a form of pain that starts and stops abruptly. It occurs due to muscular contractions of a hollow tube (small and large intestine, gall bladder, ureter, etc.) in an attempt to relieve an obstruction by forcing content out. ...

, and interstitial cystitis. It has also been used to relieve some heart problems, control some of the symptoms of

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...

, as well as for control of abnormal respiratory symptoms and "hyper-mucus secretions" in patients with lung disease. 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

and

hyoscine Scopolamine, also known as hyoscine, or Devil's Breath, is a natural or synthetically produced tropane alkaloid and anticholinergic drug that is formally used as a medication for treating motion sickness and postoperative nausea and vomi ...

and other members of the anticholinergic drug group like

cyclobenzaprine Cyclobenzaprine (sold under the brand name Flexeril, among others) is a medication used for muscle spasms from musculoskeletal conditions of sudden onset. It is not useful in cerebral palsy. It is taken by mouth. Use is not recommended for mor ...

trihexyphenidyl Trihexyphenidyl (THP, benzhexol, trihex, marketed as Artane and others) 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 Pa ...

, and

orphenadrine Orphenadrine (sold under many brand names) 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 i ...

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.

Adverse effects

Side effects include dry mouth and throat, increased appetite leading to weight gain, eye pain, blurred vision, restlessness, dizziness,

arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adult ...

, 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

but weaker than those of

, as well as dicycloverine,

, and ethanolamine antihistamines like

phenyltoloxamine Phenyltoloxamine is an antihistamine with sedative and analgesic effects. It is available in combination with other drugs such as paracetamol (acetominophen). Common use Phenyltoloxamine is widely used in preparations as an enhancing agent fo ...

Pharmacology

Hyoscyamine is an antimuscarinic; i.e., an antagonist of

muscarinic acetylcholine receptor Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end- ...

s. It blocks the action of

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

at sweat glands (sympathetic) and at

parasympathetic The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of ...

sites in salivary glands, stomach secretions, heart muscle, sinoatrial node, smooth muscle in the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

, and the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

. It increases cardiac output and heart rate, lowers blood pressure and dries secretions. It may antagonize

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...

. At comparable doses, hyoscyamine has 98 per cent of the anticholinergic power of

. The other major belladonna-derived drug

(known in the United States as Scopolamine) has 92 per cent of the antimuscarinic potency of atropine.

Biosynthesis in plants

Hyoscyamine can be extracted from plants of the family Solanaceae, notably '' Datura stramonium''. As hyoscyamine is a direct

precursor Precursor or Precursors may refer to: * Precursor (religion), a forerunner, predecessor ** The Precursor, John the Baptist Science and technology * Precursor (bird), a hypothesized genus of fossil birds that was composed of fossilized parts of u ...

in the plant biosynthesis of hyoscine, it is produced via the same

metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical ...

. The

biosynthesis Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecul ...

of hyoscine begins with the

decarboxylation Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is ...

of ''L''- ornithine to

putrescine Putrescine is an organic compound with the formula (CH2)4(NH2)2. It is a colorless solid that melts near room temperature. It is classified as a diamine. Together with cadaverine, it is largely responsible for the foul odor of putrefying flesh ...

ornithine decarboxylase The enzyme ornithine decarboxylase (, ODC) catalyzes the decarboxylation of ornithine (a product of the urea cycle) to form putrescine. This reaction is the committed step in polyamine synthesis. In humans, this protein has 461 amino acids and f ...

EC 4.1.1.17
. Putrescine is methylated to ''N''-methylputrescine by putrescine ''N''-methyltransferase
EC 2.1.1.53
. A

putrescine oxidase In enzymology, a putrescine oxidase () is an enzyme that catalyzes the chemical reaction :putrescine + O2 + H2O \rightleftharpoons 4-aminobutanal + NH3 + H2O2 The 3 substrates of this enzyme are putrescine, O2, and H2O, whereas its 3 produc ...

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 Hygrine is a pyrrolidine alkaloid, found mainly in coca leaves (0.2%). It was first isolated by Carl Liebermann in 1889 (along with a related compound cuscohygrine) as an alkaloid accompanying cocaine Cocaine (from , from , ultimately f ...

. No enzymatic activity could be demonstrated that catalyzes this reaction. Hygrine further rearranges to tropinone. Subsequently, tropinone reductase I
EC 1.1.1.206
converts tropinone to tropine which condenses with

phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amin ...

-derived phenyllactate to littorine. A

cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...

classified as Cyp80F1 oxidizes and rearranges littorine to hyoscyamine

aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl gro ...

Bush medicine basis

bush medicine Bush medicine comprises traditional medicines used by Indigenous Australians, being Aboriginal and Torres Strait Islander people. Indigenous people have been using various components of native Australian flora and some fauna as medicine for ...

developed by Aboriginal peoples of the eastern states of Australia from the soft corkwood tree, or ''

Duboisia myoporoides ''Duboisia myoporoides'', or corkwood, is a shrub or tree native to high-rainfall areas on the margins of rainforest in eastern Australia. It has a thick and corky bark. The leaves are obovate to elliptic in shape, 4–15 cm long and 1–4 ...

'', was used by the

Allies An alliance is a relationship among people, groups, or states that have joined together for mutual benefit or to achieve some common purpose, whether or not explicit agreement has been worked out among them. Members of an alliance are called ...

in World War II to stop soldiers getting seasick when they sailed across the

English Channel The English Channel, "The Sleeve"; nrf, la Maunche, "The Sleeve" ( Cotentinais) or ( Jèrriais), ( Guernésiais), "The Channel"; br, Mor Breizh, "Sea of Brittany"; cy, Môr Udd, "Lord's Sea"; kw, Mor Bretannek, "British Sea"; nl, Het Ka ...

during the

Invasion of Normandy Operation Overlord was the codename for the Battle of Normandy, the Allied operation that launched the successful invasion of German-occupied Western Europe during World War II. The operation was launched on 6 June 1944 (D-Day) with the Norm ...

. Later, it was found that the same substance could be used in the production of

scopolamine Scopolamine, also known as hyoscine, or Devil's Breath, is a natural or synthetically produced tropane alkaloid and anticholinergic drug that is formally used as a medication for treating motion sickness and postoperative nausea and vomi ...

and hyoscyamine, which are used in

eye surgery Eye surgery, also known as ophthalmic or ocular surgery, is surgery performed on the eye or its adnexa, by an ophthalmologist or sometimes, an optometrist. Eye surgery is synonymous with ophthalmology. The eye is a very fragile organ, and requ ...

, and a multi-million dollar industry was built in

Queensland ) , nickname = Sunshine State , image_map = Queensland in Australia.svg , map_caption = Location of Queensland in Australia , subdivision_type = Country , subdivision_name = Australia , established_title = Before federation , establishe ...

based on this substance.

References

{{Muscarinic acetylcholine receptor modulators Tropane alkaloids Muscarinic antagonists Antispasmodics Oneirogens Tropane alkaloids found in Solanaceae Carboxylate esters Entheogens Plant toxins