Scopolamine, also known as hyoscine, or Devil's Breath, is a

natural Nature, in the broadest sense, is the physical world or universe. "Nature" can refer to the phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. Although humans are ...

or synthetically produced

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 alkaloid ...

and

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 sys ...

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...

that is formally used as a medication for treating

motion sickness Motion sickness occurs due to a difference between actual and expected motion. Symptoms commonly include nausea, vomiting, cold sweat, headache, dizziness, tiredness, loss of appetite, and increased salivation. Complications may rarely include de ...

and

postoperative nausea and vomiting Postoperative nausea and vomiting (PONV) is the phenomenon of nausea, vomiting, or retching experienced by a patient in the postanesthesia care unit (PACU) or within 24 hours following a surgical procedure. PONV affects about 10% of the population ...

. It is also sometimes used before surgery to decrease

saliva Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be ...

. 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 A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream. An advantage of a transdermal drug delivery route over other types of medica ...

since it has been long known to have transdermal

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. Ho ...

Scopolamine is in the

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 th ...

family of drugs and works by blocking some of the effects 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 ...

within the

nervous system In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...

. Scopolamine was first written about in 1881 and started to be used for

anesthesia Anesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prevention of pain), paralysis (muscle relaxation), ...

around 1900. Scopolamine is also the main active component produced by certain plants of the

nightshade family 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 orna ...

, which historically have been used as psychoactive drugs (known as ''

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

'') due to their antimuscarinic-induced

hallucinogenic Hallucinogens are a large, diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categorized ...

effects in higher doses. In these contexts, its mind-altering effects have been utilized for

recreational Recreation is an activity of leisure, leisure being discretionary time. The "need to do something for recreation" is an essential element of human biology and psychology. Recreational activities are often done for enjoyment, amusement, or pleasur ...

, criminal and

occult The occult, in the broadest sense, is a category of esoteric supernatural beliefs and practices which generally fall outside the scope of religion and science, encompassing phenomena involving otherworldly agency, such as magic and mysticism a ...

purposes. The name "scopolamine" is derived from one type of nightshade known as ''

Scopolia ''Scopolia'' is a genus of four species of flowering plants in the family Solanaceae, native to Europe and Asia. The genus is named after Giovanni Scopoli (1723–88), a Tyrolean naturalist. The genus has a disjunct distribution, with two reco ...

'', while the name "hyoscine" is derived from another type known as ''

Hyoscyamus niger ''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. Histor ...

''. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

Medical uses

Scopolamine has a number of formal uses in modern medicine where it is used in its isolated form and in low doses to treat: *

Postoperative nausea and vomiting Postoperative nausea and vomiting (PONV) is the phenomenon of nausea, vomiting, or retching experienced by a patient in the postanesthesia care unit (PACU) or within 24 hours following a surgical procedure. PONV affects about 10% of the population ...

. *

Motion sickness Motion sickness occurs due to a difference between actual and expected motion. Symptoms commonly include nausea, vomiting, cold sweat, headache, dizziness, tiredness, loss of appetite, and increased salivation. Complications may rarely include de ...

, including

sea sickness Motion sickness occurs due to a difference between actual and expected motion. Symptoms commonly include nausea, vomiting, cold sweat, headache, dizziness, tiredness, loss of appetite, and increased salivation. Complications may rarely include d ...

, leading to its use by scuba divers (where it is often applied as a transdermal patch behind the ear) *

Gastrointestinal 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 ...

spasms *

Renal The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...

biliary A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates. Bile is required for the digestion of food and is secreted by the liver into passages that carry bile toward the hepatic duct. It ...

spasms * Aid in gastrointestinal

radiology Radiology ( ) is the medical discipline that uses medical imaging to diagnose diseases and guide their treatment, within the bodies of humans and other animals. It began with radiography (which is why its name has a root referring to radiat ...

and

endoscopy An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior of a hollow organ or cavity of the body. Unlike many other medical imaging techniques, endoscopes are insert ...

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 ...

Clozapine Clozapine is a psychiatric medication and is the first atypical antipsychotic (also called second-generation antipsychotic). It is primarily used to treat people with schizophrenia and schizoaffective disorders who have had an inadequate respo ...

-induced

drooling Drooling, or slobbering, is the flow of saliva outside the mouth. Drooling can be caused by excess production of saliva, inability to retain saliva within the mouth (incontinence of saliva), or problems with swallowing (dysphagia or odynophagia ...

Bowel 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 ...

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. ...

* Eye

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

It is sometimes used as a

premedication Premedication is using medication before some other therapy (usually surgery or chemotherapy) to prepare for that forthcoming therapy. Typical examples include premedicating with a sedative or analgesic before surgery; using prophylactic (prevent ...

, (especially to reduce respiratory tract

secretions 440px Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classica ...

) in

surgery Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pat ...

, most commonly by

injection Injection or injected may refer to: Science and technology * Injective function, a mathematical function mapping distinct arguments to distinct values * Injection (medicine), insertion of liquid into the body with a syringe * Injection, in broadca ...

. Common side effects include sleepiness, blurred vision,

dilated pupils Mydriasis is the dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, trauma, or the use of certain types of drugs. Normally, as ...

, and dry mouth. It is not recommended in people with angle-closure

glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...

or bowel obstruction. Whether its use during pregnancy is safe remains unclear, and use during

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...

is still cautioned by health professionals and manufacturers of the drug.

Breastfeeding

Scopolamine enters breast milk by secretion. Although no human studies exist to document the safety of scopolamine while nursing, the manufacturer recommends that caution be taken if scopolamine is administered to a breastfeeding woman.

Elderly

The likelihood of experiencing adverse effects from scopolamine is increased in the elderly, relative to younger people. This phenomenon is especially true for older people who are also on several other medications. Scopolamine use should be avoided in this age group because of these potent anticholinergic adverse effects, which have also been linked to an increased risk for

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

Adverse effects

Adverse effect incidence: Uncommon (0.1–1% incidence) adverse effects include: *

Dry mouth Xerostomia, also known as dry mouth, is dryness in the mouth, which may be associated with a change in the composition of saliva, or reduced salivary flow, or have no identifiable cause. This symptom is very common and is often seen as a side eff ...

Anhidrosis Hypohidrosis is a disorder in which a person exhibits diminished sweating in response to appropriate stimuli. In contrast with hyp''er''hidrosis, which is a socially troubling yet often benign condition, the consequences of untreated hypohidrosi ...

(reduced ability to sweat to cool off) *

Tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...

(usually occurs at higher doses and is succeeded by bradycardia) * Bradycardia *

Urticaria Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-last ...

(hives) *

Pruritus Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...

(itching) Rare (<0.1% incidence) adverse effects include: *

Constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...

Urinary retention Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include loss of bladd ...

Hallucination A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinati ...

s * Agitation * Confusion * Restlessness *

Seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...

s Unknown frequency adverse effects include: * Anaphylactic shock or

reactions Reaction may refer to a process or to a response to an action, event, or exposure: Physics and chemistry *Chemical reaction *Nuclear reaction *Reaction (physics), as defined by Newton's third law *Chain reaction (disambiguation). Biology and me ...

Dyspnea Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing di ...

(shortness of breath) * Rash *

Erythema Erythema (from the Greek , meaning red) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not asso ...

* Other hypersensitivity reactions * Blurred vision * Mydriasis (dilated pupils) *

Drowsiness Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...

Dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...

Somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...

Overdose

Physostigmine Physostigmine (also known as eserine from ''éséré'', the West African name for the Calabar bean) is a highly toxic parasympathomimetic alkaloid, specifically, a reversible cholinesterase inhibitor. It occurs naturally in the Calabar bean and ...

, a cholinergic drug that readily crosses the blood–brain barrier, has been used as an antidote to treat the

central nervous system depression Central nervous system (CNS) depression is a physiological state that can result in a decreased rate of breathing, decreased heart rate, and loss of consciousness possibly leading to coma or death. It is the result of inhibited or suppressed brai ...

symptoms of a scopolamine overdose. Other than this

supportive treatment Symptomatic treatment, supportive care, supportive therapy, or palliative treatment is any medical therapy of a disease that only affects its symptoms, not the underlying cause. It is usually aimed at reducing the signs and symptoms for the comfo ...

gastric lavage Gastric lavage, also commonly called stomach pumping or gastric irrigation, is the process of cleaning out the contents of the stomach. Since its first recorded use in early 19th century, it has become one of the most routine means of eliminating ...

and induced

emesis Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteriti ...

(vomiting) are usually recommended as treatments for oral overdoses. The symptoms of overdose include: * Tachycardia * Arrhythmia * Blurred vision *

Photophobia Photophobia is a medical symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of ...

paradoxical reaction A paradoxical reaction (or paradoxical effect) is an effect of a chemical substance, such as a medical drug, that is opposite to what would usually be expected. An example of a paradoxical reaction is pain caused by a pain relief medication. Parad ...

, which can present with hallucinations * Cheyne-Stokes respiration * Dry mouth * Skin reddening * Inhibition of

gastrointestinal motility Gastrointestinal physiology is the branch of human physiology that addresses the physical function of the gastrointestinal (GI) tract. The function of the GI tract is to process ingested food by mechanical and chemical means, extract nutrients and ...

Interactions

Due to interactions with metabolism of other drugs, scopolamine can cause significant unwanted side effects or unpredictable

synergies Synergy is an interaction or cooperation giving rise to a whole that is greater than the simple sum of its parts. The term ''synergy'' comes from the Attic Greek word συνεργία ' from ', , meaning "working together". History In Christian ...

when taken with other medications or compounds. Specific attention should be paid to other medications in the same pharmacologic class as scopolamine, also known as

s. These additional compounds could also potentially interact with the metabolism of scopolamine: receptor-binding

analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

/pain medication such as

gabapentinoids Gabapentinoids, also known as α2δ ligands, are a class of drugs that are chemical derivative, derivatives of the inhibitory neurotransmitter gamma-Aminobutyric acid (GABA) (i.e., GABA analogues) which channel blocker, block Voltage-dependent c ...

or opioids,

ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...

cannabinoids Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...

zolpidem Zolpidem, sold under the brand name Ambien, among others, is a medication primarily used for the short-term treatment of sleeping problems. Guidelines recommend that it be used only after cognitive behavioral therapy for insomnia and behavior ...

thiazide diuretics Thiazide () refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The first ...

nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...

, benzodiazepines,

buprenorphine Buprenorphine is an opioid used to treat opioid use disorder, acute pain, and chronic pain. It can be used under the tongue (sublingual), in the cheek (buccal), by injection (intravenous and subcutaneous), as a skin patch (transdermal ...

, and especially anticholinergic drugs such as

tiotropium Tiotropium bromide, sold under the brand name Spiriva among others, is a long-acting bronchodilator (LAMA: long acting muscarinic antagonist) used in the management of chronic obstructive pulmonary disease (COPD) and asthma. Specifically it is ...

diphenhydramine Diphenhydramine (DPH) is an antihistamine and sedative mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremor in parkinsonism, and nausea. It is taken by mouth, injected into ...

dimenhydrinate Dimenhydrinate, sold under the brand name Dramamine, among others, is an over-the-counter drug used to treat motion sickness and nausea. Dimenhydrinate is a theoclate salt composed of diphenhydramine, an ethanolamine derivative, and 8-chloroth ...

, etc. Nicotine in particular likely has a counteracting effect on the effects of scopolamine due to its opposing effect on the cholinergic system.

Route of administration

Scopolamine can be taken

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

subcutaneously The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The types of cells found in the layer are fibroblasts, adipose cells, and macro ...

, in the eye, and

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

ly, as well as via a

Pharmacokinetic

Scopolamine undergoes first-pass metabolism and about 2.6% is excreted unchanged in urine. Grapefruit juice decreases metabolism of scopolamine, consequently increasing plasma concentration.

Pharmacodynamics

Scopolamine is a nonspecific muscarinic antagonist at all four

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-rec ...

s (M1, M2, M3, and M4).,

Biosynthesis in plants

Scopolamine is among the

secondary metabolites 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 nor ...

of plants from

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 ...

(nightshade) family of plants, such as

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. ...

(''Hyoscyamus niger''), jimson weed (''

Datura ''Datura'' is a genus of nine species of highly poisonous, vespertine-flowering plants belonging to the nightshade family Solanaceae. They are commonly known as thornapples or jimsonweeds, but are also known as devil's trumpets (not to be conf ...

''), angel's trumpets (''

Brugmansia ''Brugmansia'' is a genus of seven species of flowering plants in the nightshade family Solanaceae. They are woody trees or shrubs, with pendulous flowers, and have no spines on their fruit. Their large, fragrant flowers give them their common ...

''), deadly nightshade ('' Belladonna''), mandrake (''

Mandragora officinarum ''Mandragora officinarum'' is the type species of the plant genus '' Mandragora'' in the nightshade family Solanaceae. It is often known as mandrake, although this name is also used for other plants. , sources differed significantly in the specie ...

''), and corkwood (''

Duboisia :''The orchid genus described by Karsten as ''Duboisia'' is now included in '' Myoxanthus. For the prehistoric antelope genus, see '' Duboisia (antelope).'' ''Duboisia'' (commonly called corkwood tree) is a genus of small perennial shrubs and tr ...

'').

The biosynthesis of scopolamine begins with the decarboxylation 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 a ...

. 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 In enzymology, a putrescine N-methyltransferase () is an enzyme that catalyzes the chemical reaction :S-adenosyl-L-methionine + putrescine \rightleftharpoons S-adenosyl-L-homocysteine + N-methylputrescine Thus, the two substrates of this enzym ...

. A putrescine oxidase 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 ...

of this compound to 4-methylaminobutanal, which then undergoes a spontaneous ring formation to N-

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in many ...

- pyrrolium 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 sta ...

yielding hygrine. No

enzymatic Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. ...

activity could be demonstrated to catalyze 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 converts

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 Littorine is a tropane alkaloid found in a variety of plants including ''Datura'' and ''Atropa belladonna''. It is closely related in chemical structure to atropine, hyoscyamine, and Hyoscine hydrobromide, scopolamine, which all share a common bi ...

. 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 ...

. In the final step, hyoscyamine undergoes

epoxidation In organic chemistry, an epoxide is a cyclic ether () with a three-atom ring. This ring approximates an equilateral triangle, which makes it strained, and hence highly reactive, more so than other ethers. They are produced on a large scale ...

catalyzed by 6beta-hydroxyhyoscyamine epoxidase yielding scopolamine. Scopolamine biosynthesis

History

Plants naturally containing scopolamine such as '' Atropa belladonna'' (deadly nightshade), ''

'' (angels trumpet), ''

'' (Jimson weed), ''

'', ''

Scopolia carniolica ''Scopolia carniolica'', the European scopolia or henbane bell, is a poisonous plant belonging to the family Solanaceae. It has dark violet flowers on long hanging stems. It grows to in height. Its toxicity derives from its high levels of tropan ...

'', '' Latua'' and ''

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– ...

'' have been known about and used for various purposes in both the

New New is an adjective referring to something recently made, discovered, or created. New or NEW may refer to: Music * New, singer of K-pop group The Boyz Albums and EPs * ''New'' (album), by Paul McCartney, 2013 * ''New'' (EP), by Regurgitator ...

and

Old World The "Old World" is a term for Afro-Eurasia that originated in Europe , after Europeans became aware of the existence of the Americas. It is used to contrast the continents of Africa, Europe, and Asia, which were previously thought of by the ...

s since ancient times.Armando T. Hunziker: ''The Genera of Solanaceae''. A.R.G. Gantner Verlag K.G., Ruggell, Liechtenstein 2001. Rätsch, Christian, ''The Encyclopedia of Psychoactive Plants: Ethnopharmacology and Its Applications'' pub. Park Street Press 2005 Being one of the earlier alkaloids isolated from plant sources, scopolamine has been in use in its purified forms (such as various salts, including hydrochloride, hydrobromide, hydroiodide, and sulfate) since its official isolation by the German scientist Albert Ladenburg in 1880, and as various preparations from its plant-based form since antiquity and perhaps prehistoric times. Following the description of the structure and activity of scopolamine by Ladenburg, the search for synthetic analogues, and methods for total synthesis, of scopolamine and

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 ...

in the 1930s and 1940s resulted in the discovery of

, an early antihistamine and the prototype of its chemical subclass of these drugs, and

pethidine Pethidine, also known as meperidine and sold under the brand name Demerol among others, is a synthetic opioid analgesic, pain medication of the phenylpiperidine class. Synthesized in 1938 as a potential anticholinergic agent by the German chemis ...

, the first fully synthetic

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...

, known as Dolantin and Demerol amongst many other trade names. In 1899, a Dr. Schneiderlin recommended the use of scopolamine and

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...

for surgical anaesthesia, and it started to be used sporadically for that purpose. The use of this combination in obstetric anesthesiology (childbirth) was first proposed by Richard von Steinbuchel in 1902 and was picked up and further developed by Carl Gauss in

Freiburg Freiburg im Breisgau (; abbreviated as Freiburg i. Br. or Freiburg i. B.; Low Alemannic: ''Friburg im Brisgau''), commonly referred to as Freiburg, is an independent city in Baden-Württemberg, Germany. With a population of about 230,000 (as o ...

Germany Germany,, officially the Federal Republic of Germany, is a country in Central Europe. It is the second most populous country in Europe after Russia, and the most populous member state of the European Union. Germany is situated betwe ...

, starting in 1903. The method, which was based on a drug

synergy Synergy is an interaction or cooperation giving rise to a whole that is greater than the simple sum of its parts. The term ''synergy'' comes from the Attic Greek word συνεργία ' from ', , meaning "working together". History In Christia ...

between both scopolamine and morphine came to be known as ''Dämmerschlaf'' ("

twilight sleep Twilight sleep (English translation of the German word ) is an amnesic state characterized by insensitivity to pain without loss of consciousness, induced by an injection of morphine and scopolamine, with the purpose of pain management during c ...

") or the "Freiburg method". It spread rather slowly, and different clinics experimented with different dosages and ingredients; in 1915, the ''Canadian Medical Association Journal'' reported, "the method asreally still in a state of development". It remained widely used in the US until the 1960s, when growing

chemophobia Chemophobia (or chemphobia or chemonoia) is an aversion to or prejudice against chemicals or chemistry. The phenomenon has been ascribed both to a reasonable concern over the potential adverse effects of synthetic chemicals, and to an irrational f ...

and a desire for more

natural childbirth Natural childbirth is childbirth without routine medical interventions, particularly anesthesia. Natural childbirth arose in opposition to the techno-medical model of childbirth that has recently gained popularity in industrialized societies. Natur ...

led to its abandonment.

Society and culture

Names

Hyoscine hydrobromide is the international nonproprietary name, and scopolamine hydrobromide is the

United States Adopted Name A United States Adopted Name (USAN) is a unique nonproprietary name assigned to a medication marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association (AMA), the United Stat ...

. Other names include ''levo''-duboisine, devil's breath, and ''burundanga''.

Australian bush medicine

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 (''

'') 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 from 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 ...

on their way to France 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, the same substance was found to be usable in the production of scopolamine and hyoscyamine, which are used in eye surgery, and a multimillion 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.

Recreational and religious use

While it has been occasionally used recreationally for its hallucinogenic properties, the experiences are often unpleasant, mentally and physically. It is also physically dangerous and officially classified as a

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

drug, so repeated recreational use is rare. In June 2008, more than 20 people were hospitalized with

psychosis Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...

in Norway after ingesting counterfeit

rohypnol Flunitrazepam, also known as Rohypnol among other names, is a benzodiazepine used to treat severe insomnia and assist with anesthesia. As with other hypnotics, flunitrazepam has been advised to be prescribed only for short-term use or by those ...

tablets containing scopolamine. In January 2018, 9 individuals were hospitalized in Perth, Western Australia, after reportedly ingesting scopolamine. However, the alkaloid scopolamine, when taken recreationally for its psychoactive effect is usually taken in the form of preparations from plants of the genera ''

'' or ''

'', often by

adolescents Adolescence () is a transitional stage of Developmental biology, physical and psychological Human development (biology), development that generally occurs during the period from puberty to adulthood (typically corresponding to the age of majo ...

young adults A young adult is generally a person in the years following adolescence. Definitions and opinions on what qualifies as a young adult vary, with works such as Erik Erikson's stages of human development significantly influencing the definition of ...

in order to achieve hallucinations and an

altered state of consciousness An altered state of consciousness (ASC), also called altered state of mind or mind alteration, is any condition which is significantly different from a normal waking state. By 1892, the expression was in use in relation to hypnosis, though there ...

induced by muscarinic antagonism. In circumstances such as these, the

intoxication Intoxication — or poisoning, especially by an alcoholic or narcotic substance — may refer to: * Substance intoxication: ** Alcohol intoxication ** LSD intoxication ** Toxidrome ** Tobacco intoxication ** Cannabis intoxication ** Cocaine i ...

is usually built on a synergistic, but even more toxic mixture of the additional alkaloids in the plants which includes

and hyoscyamine. Historically, the various plants that produce scopolamine have been used psychoactively for spiritual and magical purposes, particularly by witches in western culture and

indigenous Indigenous may refer to: *Indigenous peoples *Indigenous (ecology), presence in a region as the result of only natural processes, with no human intervention *Indigenous (band), an American blues-rock band *Indigenous (horse), a Hong Kong racehorse ...

groups throughout the

Americas The Americas, which are sometimes collectively called America, are a landmass comprising the totality of North and South America. The Americas make up most of the land in Earth's Western Hemisphere and comprise the New World. Along with th ...

such as Native American tribes like the

Chumash Chumash may refer to: *Chumash (Judaism), a Hebrew word for the Pentateuch, used in Judaism *Chumash people, a Native American people of southern California *Chumashan languages, indigenous languages of California See also *Chumash traditional n ...

. When

entheogenic Entheogens are psychoactive substances that induce alterations in perception, mood, consciousness, cognition, or behavior for the purposes of engendering spiritual development or otherwiseRätsch, Christian, ''The Encyclopedia of Psychoact ...

preparations of these plants were used, scopolamine was considered to be the main psychoactive compound and was largely responsible for the hallucinogenic effects, particularly when the preparation was made into a topical ointment (most notably

flying ointment Flying ointment is a hallucinogenic ointment said to have been used by witches in the practice of European witchcraft from at least as far back as the Early Modern period, when detailed recipes for such preparations were first recorded. Name ...

).Hansen, Harold A. The Witch's Garden pub. Unity Press 1978 Scopolamine is reported to be the only active alkaloid within these plants that can effectively be absorbed through the skin to cause effects. Different recipes for these ointments were explored in

European witchcraft Belief in witchcraft in Europe can be traced to classical antiquity and has continuous history during the Middle Ages, culminating in the Early Modern witch trials and giving rise to the fairy tale and popular culture "witch" stock character of ...

at least as far back as the Early Modern period and included multiple ingredients to help with the transdermal absorption of scopolamine (such as animal fat), as well as other possible ingredients to counteract its noxious and dysphoric effects. In Christianity, although not explicitly designated for

ritualistic A ritual is a sequence of activities involving gestures, words, actions, or objects, performed according to a set sequence. Rituals may be prescribed by the traditions of a community, including a religious community. Rituals are characterized, ...

or spiritual use; in the

Bible The Bible (from Koine Greek , , 'the books') is a collection of religious texts or scriptures that are held to be sacred in Christianity, Judaism, Samaritanism, and many other religions. The Bible is an anthologya compilation of texts of a ...

there are multiple mentions of

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 ...

which is a psychoactive and hallucinogenic plant root that contains scopolamine. It was associated with fertility power and (sexual) desire where it was yearned for by

Rachel Rachel () was a Biblical figure, the favorite of Jacob's two wives, and the mother of Joseph and Benjamin, two of the twelve progenitors of the tribes of Israel. Rachel's father was Laban. Her older sister was Leah, Jacob's first wife. Her aun ...

, who apparently was "barren" (infertile) but trying to conceive.

Interrogation

The effects of scopolamine were studied for use as a

truth serum "Truth serum" is a colloquial name for any of a range of psychoactive drugs used in an effort to obtain information from subjects who are unable or unwilling to provide it otherwise. These include ethanol, scopolamine, 3-quinuclidinyl benzilate, ...

in interrogations in the early 20th century, but because of the side effects, investigations were dropped. In 2009, the

Czechoslovak Czechoslovak may refer to: *A demonym or adjective pertaining to Czechoslovakia (1918–93) **First Czechoslovak Republic (1918–38) **Second Czechoslovak Republic (1938–39) **Third Czechoslovak Republic (1948–60) **Fourth Czechoslovak Repub ...

state security secret police were proven to have used scopolamine at least three times to obtain confessions from alleged antistate

dissident A dissident is a person who actively challenges an established political or religious system, doctrine, belief, policy, or institution. In a religious context, the word has been used since the 18th century, and in the political sense since the 20th ...

Crime in Colombia

A travel advisory published by the US Overseas Security Advisory Council (OSAC) in 2012 stated: Between 1998 and 2004, 13% of emergency-room admissions for "poisoning with criminal intentions" in a clinic of

Bogotá Bogotá (, also , , ), officially Bogotá, Distrito Capital, abbreviated Bogotá, D.C., and formerly known as Santa Fe de Bogotá (; ) during the Spanish period and between 1991 and 2000, is the capital city of Colombia, and one of the larges ...

, Colombia, have been attributed to scopolamine, and 44% to benzodiazepines. Most commonly, the person has been poisoned by a robber who gave the victim a scopolamine-laced beverage, in the hope that the victim would become unconscious or unable to effectively resist the robbery. Beside robberies, it is also allegedly involved in

express kidnapping Express kidnapping ( es, secuestro exprés; pt, sequestro relâmpago) is a method of abduction where a small immediate ransom is demanded, often by the victim being forced to withdraw money from their ATM account. Known in the United States s ...

s and

sexual assault Sexual assault is an act in which one intentionally sexually touches another person without that person's consent, or coerces or physically forces a person to engage in a sexual act against their will. It is a form of sexual violence, which ...

. The Hospital Clínic in

Barcelona Barcelona ( , , ) is a city on the coast of northeastern Spain. It is the capital and largest city of the autonomous community of Catalonia, as well as the second most populous municipality of Spain. With a population of 1.6 million within ci ...

introduced a

protocol Protocol may refer to: Sociology and politics * Protocol (politics), a formal agreement between nation states * Protocol (diplomacy), the etiquette of diplomacy and affairs of state * Etiquette, a code of personal behavior Science and technolog ...

in 2008 to help medical workers identify cases, while Madrid hospitals adopted a similar working document in February 2015. Hospital Clínic has found little scientific evidence to support this use and relies on the victims' stories to reach any conclusion. Although poisoning by scopolamine appears quite often in the media as an aid for raping, kidnapping, killing, or robbery, the effects of this drug and the way it is applied by criminals (transdermal injection, on playing cards and papers, etc.) are often exaggerated, especially skin exposure, as the dose that can be absorbed by the skin is too low to have any effect. Scopolamine transdermal patches must be used for hours to days. There are certain other aspects of the usage of scopolamine in crimes. Powdered scopolamine is referred to as "devil's breath". In popular media and television, it is portrayed as a method to

brainwash Brainwashing (also known as mind control, menticide, coercive persuasion, thought control, thought reform, and forced re-education) is the concept that the human mind can be altered or controlled by certain psychological techniques. Brainwashin ...

or control people into being defrauded by their attackers; there is debate whether these claims are true. It is not verified if the powdered form is capable of inducing a suggestive state. The danger is real enough that in addition to the Overseas Security Advisory Council (OSAC) in 2012, the US Department of State, as well as the Government of Canada, published travel advisories warning travelers about the possibility of targeting. Criminals using Devil’s Breath often use attractive, young women to target men that they believe are wealthy. Nevertheless, the drug is known to produce loss of memory following exposure and

sleepiness Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...

, similar to the effect of benzodiazepines or

alcohol poisoning Alcohol intoxication, also known as alcohol poisoning, commonly described as drunkenness or inebriation, is the negative behavior and physical effects caused by a recent consumption of alcohol. In addition to the toxicity of ethanol, the main ps ...

Research

Scopolamine is used as a research tool to study memory encoding. Initially, in human trials, relatively low doses of the muscarinic receptor antagonist scopolamine were found to induce temporary cognitive defects. Since then, scopolamine has become a standard drug for experimentally inducing cognitive defects in animals. Results in primates suggest that

is involved in the encoding of new information into long-term memory. Scopolamine has also been shown to exert a greater impairment on

episodic memory Episodic memory is the memory of everyday events (such as times, location geography, associated emotions, and other contextual information) that can be explicitly stated or conjured. It is the collection of past personal experiences that occurred ...

, event-related potentials,

memory retention 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 remembered, ...

and

free recall Free recall is a common task in the psychological study of memory. In this task, participants study a list of items on each trial, and then are prompted to recall the items in any order. Items are usually presented one at a time for a short d ...

compared to DPH (an anticholinergic and

antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provid ...

). Scopolamine produces detrimental effects on short-term memory, memory acquisition, learning, visual recognition memory, visuospatial praxis, visuospatial memory, visuoperceptual function,

verbal recall Verbal memory is a term used in cognitive psychology which refers to memory of words and other abstractions involving language. Verbal encoding Verbal encoding refers to the interpretation of verbal stimuli. Verbal encoding appears to be strongly ...

, and psychomotor speed. It does not seem to impair recognition and memory retrieval, though. Acetylcholine projections in hippocampal neurons, which are vital in mediating long-term potentiation, are inhibited by scopolamine. Scopolamine also inhibits cholinergic-mediated glutamate release in hippocampal neurons, which assist in depolarization, potentiation of action potential, and synaptic suppression. Scopolamine's effects on acetylcholine and glutamate release in the hippocampus favor retrieval-dominant cognitive functioning. Scopolamine has been used to model the defects in cholinergic function for models of Alzheimer's, dementia, fragile X syndrome, and Down syndrome. Scopolamine has been identified as a psychoplastogen, which refers to a compound capable of promoting rapid and sustained

neuroplasticity Neuroplasticity, also known as neural plasticity, or brain plasticity, is the ability of Neural circuit, neural networks in the brain to change through growth and reorganization. It is when the brain is rewired to function in some way that diffe ...

in a single dose. It has been, and continues to be investigated as a rapid-onset

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

, with a number of small studies finding positive results, particularly in female subjects.

NASA The National Aeronautics and Space Administration (NASA ) is an independent agency of the US federal government responsible for the civil space program, aeronautics research, and space research. NASA was established in 1958, succeeding t ...

agreed to develop a nasal administration method. With a precise dosage, the NASA spray formulation has been shown to work faster and more reliably than the oral form to treat motion sickness. Although a fair amount of research has been applied to scopolamine in the field of medicine, its

(psychoactive) effects as well as the psychoactive effects of other anticholinergic

hasn’t been extensively researched or as well understood compared to other types of hallucinogens such as psychedelic and disassociative compounds, despite the alkaloid’s long history of usage in mind-altering plant preparations.

References

External links

* * {{Authority control Carboxylate esters Deliriants Entheogens Epoxides Motion sickness Muscarinic antagonists Plant toxins Tropane alkaloids found in Solanaceae Tropane alkaloids Wikipedia medicine articles ready to translate World Health Organization essential medicines