Hyoscyamine (also known as daturine or duboisine) is a naturally occurring

tropane alkaloid Tropane alkaloids are a class of bicyclic .2.1alkaloids 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 alkal ...

and plant toxin. It is a

secondary metabolite Secondary metabolites, also called specialised metabolites, toxins, secondary products, or natural products, are organic compounds produced by any lifeform, e.g. bacteria, fungi, animals, or plants, which are not directly involved in the norm ...

found in certain plants of the family

Solanaceae The Solanaceae , or nightshades, are a family of flowering plants that ranges from annual and perennial herbs to vines, lianas, epiphytes, shrubs, and trees, and includes a number of agricultural crops, medicinal plants, spices, weeds, and orn ...

, including

henbane ''Hyoscyamus niger'', commonly known as henbane, black henbane, or stinking nightshade, is a poisonous plant in the nightshade family Solanaceae. It is native to temperate Europe and Siberia, and naturalised in Great Britain and Ireland. ...

mandrake A mandrake is the root of a plant, historically derived either from plants of the genus '' Mandragora'' found in the Mediterranean region, or from other species, such as ''Bryonia alba'', the English mandrake, which have similar properties. The ...

, angel's trumpets,

jimsonweed ''Datura stramonium'', known by the common names thorn apple, jimsonweed (jimson weed), devil's snare, or devil's trumpet, is a poisonous flowering plant of the nightshade family Solanaceae. It is a species belonging to the ''Datura'' genus a ...

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 ''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 eggplant (aubergine). It is native to Europe, North ...

. 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. Iso ...

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 i ...

(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 ulcer Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines i ...

irritable bowel syndrome Irritable bowel syndrome (IBS) is a "disorder of gut-brain interaction" characterized by a group of symptoms that commonly include abdominal pain and or abdominal bloating and changes in the consistency of bowel movements. These symptoms may ...

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 abdominal ...

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 pancr ...

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 Interstitial cystitis (IC), a type of bladder pain syndrome (BPS), is chronic pain in the bladder and pelvic floor of unknown cause. It is the urologic chronic pelvic pain syndrome of women. Symptoms include feeling the need to urinate right awa ...

. 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 becom ...

, 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 vomiti ...

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 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 Ileus is a disruption of the normal propulsive ability of the intestine. It can be caused by lack of peristalsis or by mechanical obstruction. The word 'ileus' is from Ancient Greek ''eileós'' (, "intestinal obstruction"). The term 'subileus' re ...

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 adults ...

, 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 Dicycloverine, also known as dicyclomine, sold under the brand name Bentyl in the US, is a medication that is used to treat spasms of the intestines such as occur in irritable bowel syndrome. It is taken by mouth or by injection into a muscle. ...

, orphenadrine,

, 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 f ...

Pharmacology

Hyoscyamine is an

antimuscarinic A muscarinic receptor antagonist (MRA) 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 ...

; 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-rece ...

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. Part ...

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 t ...

sites in salivary glands, stomach secretions, heart muscle,

sinoatrial node The sinoatrial node (also known as the sinuatrial node, SA node or sinus node) is an oval shaped region of special cardiac muscle in the upper back wall of the right atrium made up of cells known as pacemaker cells. The sinus node is approximat ...

, 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 organ (biology), organs of the digestive syste ...

, 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 par ...

. 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 vas ...

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

anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous system ...

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

, notably ''

Datura stramonium ''Datura stramonium'', known by the common names thorn apple, jimsonweed (jimson weed), devil's snare, or devil's trumpet, is a poisonous flowering plant of the nightshade family Solanaceae. It is a species belonging to the ''Datura'' genus a ...

''. 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 reac ...

. 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 macromolecules. ...

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 t ...

of ''L''-

ornithine Ornithine is a non-proteinogenic amino acid that plays a role in the urea cycle. Ornithine is abnormally accumulated in the body in ornithine transcarbamylase deficiency. The radical is ornithyl. Role in urea cycle L-Ornithine is one of the produ ...

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, b ...

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 fo ...

EC 4.1.1.17
. Putrescine is

methylated In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These ...

to ''N''-methylputrescine by putrescine ''N''-methyltransferase
EC 2.1.1.53
. A putrescine oxidase
EC 1.4.3.10
that specifically recognizes methylated putrescine catalyzes the

deamination Deamination is the removal of an amino group from a molecule. Enzymes that catalyse this reaction are called deaminases. In the human body, deamination takes place primarily in the liver, however it can also occur in the kidney. In situations of e ...

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 Acetoacetic acid (also acetoacetate and diacetic acid) is the organic compound with the formula CHCOCHCOOH. It is the simplest beta-keto acid, and like other members of this class, it is unstable. The methyl and ethyl esters, which are quite stab ...

yielding hygrine. No enzymatic activity could be demonstrated that catalyzes this reaction. Hygrine further rearranges to

tropinone Tropinone is an alkaloid, famously synthesised in 1917 by Robert Robinson as a synthetic precursor to atropine, a scarce commodity during World War I. Tropinone and the alkaloids cocaine and atropine all share the same tropane core structure. It ...

. Subsequently, tropinone reductase I
EC 1.1.1.206
converts tropinone to

tropine Tropine is a derivative of tropane containing a hydroxyl group at the third carbon. It is also called 3-tropanol. Tropine is a central building block of many chemicals active in the nervous system, including tropane alkaloids. Some of these comp ...

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 amino a ...

-derived phenyllactate to littorine. A

cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...

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 grou ...

Bush medicine basis

A bush medicine developed by

Aboriginal peoples Indigenous peoples are culturally distinct ethnic groups whose members are directly descended from the earliest known inhabitants of a particular geographic region and, to some extent, maintain the language and culture of those original people ...

of the

eastern states of Australia The eastern states of Australia are the states adjoining the east continental coastline of Australia. These are the mainland states of Victoria, New South Wales and Queensland, and the island state of Tasmania. The Australian Capital Territor ...

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– ...

'', 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 Kana ...

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 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 , established_ ...

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