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 alkaloi ...

and plant toxin. It is a

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

found in certain plants of the family

Solanaceae Solanaceae (), commonly known as the nightshades, is a family of flowering plants in the order Solanales. It contains approximately 2,700 species, several of which are used as agricultural crops, medicinal plants, and ornamental plants. Many me ...

, including

henbane Henbane (''Hyoscyamus niger'', also black henbane and stinking nightshade) is a poisonous plant belonging to tribe Hyoscyameae of the nightshade family ''Solanaceae''. Henbane is native to Temperate climate, temperate Europe and Siberia, and natu ...

mandrake A mandrake is the root of a plant, historically derived either from plants of the genus '' Mandragora'' (in the family Solanaceae) found in the Mediterranean region, or from other species, such as '' Bryonia alba'' (the English mandrake, in the ...

, angel's trumpets, jimsonweed, the sorcerers' tree, and

Atropa belladonna ''Atropa bella-donna'', commonly known as deadly nightshade or belladonna, is a toxic perennial herbaceous plant in the nightshade family Solanaceae, which also includes tomatoes, potatoes and eggplant. It is native to Europe and Western Asia, i ...

(deadly nightshade). It is the levorotary

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formula – that is, the same number of atoms of each element (chemistry), element – but distinct arrangements of atoms in space. ''Isomerism'' refers to the exi ...

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 give ...

(third of the three major nightshade alkaloids) and thus sometimes known as levo-atropine. In 2021, it was the 272nd most commonly prescribed medication in the United States, with more than 900,000 prescriptions.

Medical uses

Hyoscyamine is used to provide symptomatic relief of spasms caused by various lower abdominal and bladder disorders including

peptic ulcer Peptic ulcer disease is when the inner part of the stomach's gastric mucosa (lining of the stomach), the first part of the small intestine, or sometimes the lower esophagus, gets damaged. An ulcer in the stomach is called a gastric ulcer, while ...

irritable bowel syndrome Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by a group of symptoms that commonly include abdominal pain, abdominal bloating, and changes in the consistency of bowel movements. These symptoms may ...

diverticulitis Diverticulitis, also called colonic diverticulitis, is a gastrointestinal disease characterized by inflammation of abnormal pouches—Diverticulum, diverticula—that can develop in the wall of the large intestine. Symptoms typically include lo ...

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 hormone A hormone (from the Ancient Greek, Greek participle , "se ...

, colic, and

interstitial cystitis Interstitial cystitis (IC), a type of bladder pain syndrome (BPS), is chronic pain in the Urinary bladder, bladder and pelvic floor of unknown cause. Symptoms include urinary urgency, feeling the need to urinate right away, urinary frequency, ...

. 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 neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...

, 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 atropine and hyoscine and other members of the anticholinergic drug group like

cyclobenzaprine Cyclobenzaprine, sold under several brand names including, historically, Flexeril, is a muscle relaxer used for muscle spasms from musculoskeletal conditions of sudden onset. It is not useful in cerebral palsy. It is taken by mouth. Common ...

, trihexyphenidyl, 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 in ...

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' derives . The term 'subileus' refers to a partial obstruction. Signs and symptoms S ...

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, are irregularities in the cardiac cycle, heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – ab ...

, 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 Dicycloverine, also known as dicyclomine, sold under the brand name Bentyl among others, is a medication that is used to treat spasms of the intestines such as those that occur in irritable bowel syndrome (IBS). It is taken by mouth or by injec ...

, trihexyphenidyl, and ethanolamine antihistamines like phenyltoloxamine.

Pharmacology

Pharmacodynamics

Hyoscyamine is an

antimuscarinic A muscarinic acetylcholine receptor antagonist, also simply known as a muscarinic antagonist or as an antimuscarinic agent, is a type of anticholinergic drug that blocks the activity of the muscarinic acetylcholine receptors (mAChRs). The muscarin ...

; i.e., an antagonist of

muscarinic acetylcholine receptor Muscarinic acetylcholine receptors (mAChRs) are acetylcholine receptors that form G protein-coupled receptor, G protein-coupled receptor complexes in the cell membranes of certain neurons and other Cell (biology), cells. They play several role ...

s. It blocks the action of

acetylcholine Acetylcholine (ACh) is an organic compound 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 autonomic nervous system is responsible for regulat ...

sites in salivary glands, stomach secretions, heart muscle,

sinoatrial node The sinoatrial node (also known as the sinuatrial node, SA node, sinus node or Keith–Flack node) is an ellipse, oval shaped region of special cardiac muscle in the upper back wall of the right atrium made up of Cell (biology), cells known as pa ...

, smooth muscle in the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

, and the

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

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

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

. At comparable doses, hyoscyamine has 98 percent of the

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

power of atropine. The other major

-derived drug hyoscine (known in the United States as scopolamine) has 92 per cent of the antimuscarinic potency of atropine. Hyoscyamine has been described as a selective muscarinic acetylcholine M₂ receptor

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain. This is in contrast to related antimuscarinics like

and scopolamine, which are non-selective antagonists of all five muscarinic acetylcholine receptors. Antagonism of both the muscarinic acetylcholine M₁ receptor and M₂ receptor has been implicated as having negative effects on

memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembe ...

and

cognition Cognition is the "mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought, ...

. Hyoscyamine has been described as having

deliriant Deliriants are a subclass of hallucinogen. The term was coined in the early 1980s to distinguish these drugs from psychedelics such as LSD and dissociatives such as ketamine, due to their primary effect of causing delirium, as opposed to th ...

effects similarly to scopolamine, atropine, and other antimuscarinics. However, other sources have reported that hyoscyamine potently antagonizes all five muscarinic acetylcholine receptor subtypes.

Biosynthesis in plants

Hyoscyamine can be extracted from plants of the family

, notably ''

Datura stramonium ''Datura stramonium'', known by the common names thornapple, jimsonweed (jimson weed), or devil's trumpet, is a poisonous flowering plant in the ''Datureae, Daturae'' Tribe (botany), tribe of the nightshade family Solanaceae. Its likely origi ...

''. As hyoscyamine is a direct precursor 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 (biology), cell. The reactants, products, and Metabolic intermediate, intermediates of an enzymatic reaction are known as metabolites, which are ...

. The

biosynthesis Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...

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 Ornithine is a non-proteinogenic α-amino acid that plays a role in the urea cycle. It is not incorporated into proteins during translation. Ornithine is abnormally accumulated in the body in ornithine transcarbamylase deficiency, a disorder of th ...

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 Putrefaction, putref ...

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 ...

EC 4.1.1.17
. Putrescine is

methylated Methylation, in the chemical sciences, is 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 term ...

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 catalysis, 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 s ...

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. 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 chemical formula, formula . It can be viewed as a benzyl group substituent, substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of ...

-derived phenyllactate to littorine. A

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

classified as Cyp80F1 oxidizes and rearranges littorine to hyoscyamine

aldehyde In organic chemistry, an aldehyde () (lat. ''al''cohol ''dehyd''rogenatum, dehydrogenated alcohol) is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred ...

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 t ...

developed by Aboriginal peoples 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 An island or isle is a piece of land, dist ...

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 The English Channel, also known as the Channel, is an arm of the Atlantic Ocean that separates Southern England from northern France. It links to the southern part of the North Sea by the Strait of Dover at its northeastern end. It is the busi ...

during the

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

. 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 Queensland ( , commonly abbreviated as Qld) is a States and territories of Australia, state in northeastern Australia, and is the second-largest and third-most populous state in Australia. It is bordered by the Northern Territory, South Austr ...

based on this substance.

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.

References

{{Authority control Antispasmodics Carboxylate esters Entheogens M2 receptor antagonists Oneirogens Plant toxins Tropane alkaloids Tropane alkaloids found in Solanaceae