Scopolamine
Encyclopedia
Scopolamine, also known as levo-duboisine, and hyoscine, is a tropane alkaloid
Tropane alkaloid
Tropane alkaloids are a class of alkaloids and secondary metabolites that contain a tropane ring in their chemical structure...

 drug
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...

 with muscarinic antagonist
Muscarinic antagonist
In neurochemistry, a muscarinic receptor antagonist is an agent that reduces the activity of the muscarinic acetylcholine receptor. Acetylcholine is a neurotransmitter, whose receptor is a protein found in synapses and other cell membranes...

 effects. It is among the secondary metabolites of plants from Solanaceae
Solanaceae
Solanaceae are a family of flowering plants that include a number of important agricultural crops as well as many toxic plants. The name of the family comes from the Latin Solanum "the nightshade plant", but the further etymology of that word is unclear...

 (nightshade) family of plants, such as henbane
Henbane
Henbane , also known as stinking nightshade or black henbane, is a plant of the family Solanaceae that originated in Eurasia, though it is now globally distributed.-Toxicity and historical usage:...

, jimson weed and Angel's Trumpets (Datura
Datura
Datura is a genus of nine species of vespertine flowering plants belonging to the family Solanaceae. Its precise and natural distribution is uncertain, owing to its extensive cultivation and naturalization throughout the temperate and tropical regions of the globe...

 resp. Brugmansia
Brugmansia
Brugmansia is a genus of seven species of flowering plants in the family Solanaceae, native to subtropical regions of South America, along the Andes from Colombia to northern Chile, and also in southeastern Brazil. They are known as Angel's Trumpets, sharing that name with the closely related genus...

 spec.), and corkwood (Duboisia
Duboisia
Duboisia is a genus of small perennial shrubs to trees about 14 m tall, with extremely light wood and a thick corky bark. There are four species; all occur in Australia, and one also occurs in New Caledonia....

 species ). Scopolamine exerts its effects by acting as a competitive antagonist at muscarinic acetylcholine receptors, specifically M1 receptors; it is thus classified as an anticholinergic
Anticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....

, anti-muscarinic drug. (See the article on the parasympathetic nervous system for details of this physiology.)

Although scopolamine is often portrayed in the media as a dangerous drug, its anticholinergic
Anticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....

 properties give it some legitimate medical applications in very minute doses. As an example, in the treatment of motion sickness
Motion sickness
Motion sickness or kinetosis, also known as travel sickness, is a condition in which a disagreement exists between visually perceived movement and the vestibular system's sense of movement...

, the dose, gradually released from a transdermal patch
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. Often, this promotes healing to an injured area of the body. An advantage of a transdermal drug delivery route over other types of...

, is only 330 microgram
Microgram
In the metric system, a microgram is a unit of mass equal to one millionth of a gram , or 1/1000 of a milligram. It is one of the smallest units of mass commonly used...

s (µg) per day. In rare cases, unusual reactions to ordinary doses of scopolamine have occurred including confusion, agitation, rambling speech, hallucinations, paranoid behaviors, and delusions.

Etymology

Scopolamine is named after the plant genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...

 Scopolia
Scopolia
Scopolia is a genus of five species of flowering plants in the family Solanaceae, native to Europe and Asia. The genus is named after Giovanni Scopoli , a Tyrolian naturalist....

. The name "hyoscine" is from the scientific name for henbane
Henbane
Henbane , also known as stinking nightshade or black henbane, is a plant of the family Solanaceae that originated in Eurasia, though it is now globally distributed.-Toxicity and historical usage:...

, Hyoscyamus niger.

Biosynthesis in plants

The biosynthesis
Biosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...

 of scopolamine begins with the decarboxylation
Decarboxylation
Decarboxylation is a chemical reaction that releases carbon dioxide . Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carbonation, the addition of CO2 to...

 of L-ornithine to putrescine
Putrescine
Putrescine is a foul-smelling organic chemical compound NH24NH2 that is related to cadaverine; both are produced by the breakdown of amino acids in living and dead organisms and both are toxic in large doses...

 by ornithine decarboxylase
Ornithine decarboxylase
The enzyme ornithine decarboxylase catalyzes the decarboxylation of ornithine to form putrescine. This reaction is the committed step in polyamine synthesis. In humans, this protein has 461 amino acids and forms a homodimer....

 (EC 4.1.1.17). Putrescine is methylated
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...

 to N-methylputrescine by putrescine N-methyltransferase
Putrescine N-methyltransferase
In enzymology, a putrescine N-methyltransferase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are S-adenosyl methionine and putrescine, whereas its two products are S-adenosylhomocysteine and N-methylputrescine....

 (EC 2.1.1.53).

A putrescine oxidase
Putrescine oxidase
In enzymology, a putrescine oxidase is an enzyme that catalyzes the chemical reactionThe 3 substrates of this enzyme are putrescine, O2, and H2O, whereas its 3 products are 4-aminobutanal, NH3, and H2O2....

 (EC 1.4.3.10) that specifically recognizes methylated purtrescine catalizes the deamination
Deamination
Deamination is the removal of an amine group from a molecule. Enzymes which catalyse this reaction are called deaminases.In the human body, deamination takes place primarily in the liver, however glutamate is also deaminated in the kidneys. Deamination is the process by which amino acids are...

 of this compound to 4-methylaminobutanal which then undergoes a spontanous ring formation to N-Methyl-pyrrolium cation. In the next step, the pyrrolium cation condenses with acetoacetic acid
Acetoacetic acid
Acetoacetic acid is the organic compound with the formula CH3CCH2CO2H. It is the simplest beta-keto acid group and like other members of this class is unstable.- Synthesis and properties :...

 yielding hygrine
Hygrine
Hygrine is a pyrrolidine alkaloid, found mainly in coca leaves . It was first isolated by Carl Liebermann in 1889 as an alkaloid accompanying cocaine in coca. Hygrine is extracted as a thick yellow oil, having a pungent taste and odor....

. No enzmyatic activity could be demonstrated that catalyzes this reaction. Hygrine further rearranges to tropinone
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.-Synthesis:...

.

Subsequently, Tropinone reductase I
Tropinone reductase I
In enzymology, a tropinone reductase I is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are tropine and NADP+, whereas its 3 products are tropinone, NADPH, and H+....

 (EC 1.1.1.206) converts tropinone to tropine
Tropine
Tropine is a derivative of tropane containing a hydroxyl group at third carbon. It is also called 3-tropanol.Benzatropine and etybenzatropine are derivatives of tropine. It is also a building block of atropine, a cholinergic drug prototypical of the muscarinic antagonist class.-External Links:*...

 which condenses with phenylalanine
Phenylalanine
Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...

-derived phenyllactate to littorine. A cytochrome P450 classified as Cyp80F1 oxidizes and rearranges littorine to hyoscyamine aldehyde
Aldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....

. In the final step, hyoscyamine
Hyoscyamine
Hyoscyamine is a tropane alkaloid. It is a secondary metabolite found in certain plants of the Solanaceae family, including henbane , mandrake , jimsonweed , tomato and deadly nightshade...

 undergoes epoxidation which is catalyzed by 6beta-hydroxyhyoscyamine epoxidase
6beta-hydroxyhyoscyamine epoxidase
In enzymology, a 6β-hydroxyhyoscyamine epoxidase is an enzyme that catalyzes the chemical reaction-6-hydroxyhyoscyamine + 2-oxoglutarate + O2 \rightleftharpoons scopolamine + succinate + CO2 + H2O...

 (EC 1.14.11.14) yielding scopolamine.

History

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 isolation by the German scientist Albert Ladenburg
Albert Ladenburg
Albert Ladenburg was a German chemist.-Biography:Ladenburg was a member of a well known Jewish family in Mannheim. He was educated at a Realgymnasium at Mannheim and then, after the age of 15, at the technical school of Karlsruhe, where he studied mathematics and modern languages...

 in 1880, and as various preparations from its plant-based form since antiquity and perhaps pre-historic times. Following the description of the structure and activity of scopolamine by Ladenburg, the search for synthetic analogues of and methods for total synthesis of scopolamine and/or atropine in the 1930s and 1940s resulted in the discovery of diphenhydramine
Diphenhydramine
Diphenhydramine hydrochloride is a first-generation antihistamine possessing anticholinergic, antitussive, antiemetic, and sedative properties which is mainly used to treat allergies. Like most other first-generation antihistamines, the drug also has a powerful hypnotic effect, and for this reason...

, an early antihistamine and the prototype of its chemical subclass of these drugs, and pethidine
Pethidine
Pethidine or meperidine Pethidine (INN) or meperidine (USAN) Pethidine (INN) or meperidine (USAN) (commonly referred to as Demerol but also referred to as: isonipecaine; lidol; pethanol; piridosal; Algil; Alodan; Centralgin; Dispadol; Dolantin; Mialgin (in Indonesia); Petidin Dolargan (in Poland);...

, the first fully synthetic opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...

 analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....

, known as Dolatin and Demerol amongst many other trade names.

Scopolamine was used in conjunction with morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...

, oxycodone
Oxycodone
Oxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. It was developed in 1916 in Germany, as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine , and codeine.Oxycodone oral medications are generally...

, or other opioids from before 1900 up into the 1960s to put mothers in labor into a kind of "twilight sleep
Twilight sleep
Twilight sleep is an amnesic condition characterized by insensibility to pain without loss of consciousness, induced by an injection of morphine and scopolamine, especially to relieve the pain of childbirth...

". The analgesia from scopolamine plus a strong opioid is deep enough to allow higher doses to be used as a form of anaesthesia.

Scopolamine mixed with oxycodone
Oxycodone
Oxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. It was developed in 1916 in Germany, as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine , and codeine.Oxycodone oral medications are generally...

 (Eukodal), and ephedrine
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....

 was marketed by Merck as SEE (from the German initials of the ingredients) and Scophedal starting in 1928, and the mixture is sometimes mixed up on site on rare occasions in the area of its greatest historical usage, namely Germany and Central Europe.

Scopolamine was also one of the active ingredients in Asthmador
Asthmador
Asthmador was a nonpresciption treatment for the relief of bronchial asthma made by the R. Schiffmann Company. It consisted of a mixture of belladonna, stramonium and potassium perchlorate, and was a fine powder intended to be burnt and the smoke inhaled...

, an over-the-counter smoking preparation marketed in the 1950s and '60s claiming to combat asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...

 and bronchitis
Bronchitis
Acute bronchitis is an inflammation of the large bronchi in the lungs that is usually caused by viruses or bacteria and may last several days or weeks. Characteristic symptoms include cough, sputum production, and shortness of breath and wheezing related to the obstruction of the inflamed airways...

. In November 1990 the U.S. Food and Drug Administration forced OTC products with scopolamine and several hundred other ingredients that had allegedly not been proven effective off the market. Scopolamine shared a small segment of the OTC sleeping pill market with diphenhydramine
Diphenhydramine
Diphenhydramine hydrochloride is a first-generation antihistamine possessing anticholinergic, antitussive, antiemetic, and sedative properties which is mainly used to treat allergies. Like most other first-generation antihistamines, the drug also has a powerful hypnotic effect, and for this reason...

, phenyltoloxamine
Phenyltoloxamine
Phenyltoloxamine is an antihistamine with sedative and analgesic effects. It is a member of the ethanolamine class of antihistaminergic agents and an anticholinergic.-Common use:...

, pyrilamine, doxylamine
Doxylamine
Doxylamine is one of the many sedating antihistamines used by itself as a short-term sedative, and in combination with other drugs as a night-time cold and allergy relief drug...

 and other first generation antihistamines, many of which are still used for this purpose in drugs like Sominex
Sominex
Sominex is a trademarked name for two over the counter sleep aids. In the United States diphenhydramine is marketed under this name by GlaxoSmithKline. In the UK Actavis UK markets Promethazine hydrochloride under the Sominex brand....

, Tylenol PM, NyQuil
NyQuil
NyQuil is a brand of over the counter medication which is intended to relieve various symptoms of the common cold. Because all of the medications within the NyQuil imprint contain sedating antihistamines, hypnotics, and/or alcohol, they are intended to be taken before sleep...

, etc.

Methods of administration

Scopolamine can be administered orally, subcutaneously, opthalmically
Eye drop
Eye drops are saline-containing drops used as a route to administer medication in the eye. Depending on the condition being treated, they may contain steroids, antihistamines, sympathomimetics, beta receptor blockers, parasympathomimetics, parasympatholytics, prostaglandins, non-steroidal...

 and intravenously, as well as via a transdermal patch
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. Often, this promotes healing to an injured area of the body. An advantage of a transdermal drug delivery route over other types of...

. The transdermal patch (e.g. Transderm Scōp) for prevention of nausea and motion sickness employs scopolamine base, and is effective for up to 3 days. The oral, ophthalmic and intravenous forms have shorter half-lives
Half-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...

 and are usually found in the form scopolamine hydrobromide (for example in Scopace, soluble 0.4 mg tablets or Donnatal
Donnatal
Donnatal is a proprietary combination medication for the treatment of intestinal cramping due to various causes, often administered as part of a GI Cocktail. It is classed as an anticholinergic antispasmodic drug. Donnatal is marketed by PBM Pharmaceuticals. It is available as tablets, capsules,...

).

Medical use

Scopolamine has a number of uses in medicine
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....

:
  • Primary Uses:
    • Treatment of nausea
      Nausea
      Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

       and motion sickness
      Motion sickness
      Motion sickness or kinetosis, also known as travel sickness, is a condition in which a disagreement exists between visually perceived movement and the vestibular system's sense of movement...

      .
    • Treatment of intestinal cramping.
    • For ophthalmic purposes.
    • As a general depressant and adjunct to narcotic painkillers.

  • Secondary Uses:
    • As a preanesthetic agent
      Preanesthetic agent
      A preanesthetic agent is a drug that is given before the administration of an anesthetic.-Examples:Examples of preanesthetic agents are:*Acepromazine *atropine *diazepam *Scopolamine...

      .
    • As a drying agent for sinuses, lungs, and related areas.
    • To reduce motility and secretions in the GI tract—most frequently in tinctures or other belladonna or stramonium preparations, often used in conjunction with other drugs as in Donnagel original forumulation, Donnagel-PG (with paregoric
      Paregoric
      Paregoric, or camphorated tincture of opium, also known as tinctura opii camphorata, is a medication known for its antidiarrheal, antitussive, and analgesic properties.-History:...

      ), Donnabarb/Barbadonna/Donnatal
      Donnatal
      Donnatal is a proprietary combination medication for the treatment of intestinal cramping due to various causes, often administered as part of a GI Cocktail. It is classed as an anticholinergic antispasmodic drug. Donnatal is marketed by PBM Pharmaceuticals. It is available as tablets, capsules,...

       (with phenobarbital
      Phenobarbital
      Phenobarbital or phenobarbitone is a barbiturate, first marketed as Luminal by Friedr. Bayer et comp. It is the most widely used anticonvulsant worldwide, and the oldest still commonly used. It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the...

      ), and a number of others.
    • Uncommonly, for some forms of Parkinsonism
      Parkinsonism
      Parkinsonism is a neurological syndrome characterized by tremor, hypokinesia, rigidity, and postural instability. The underlying causes of parkinsonism are numerous, and diagnosis can be complex...

      .
    • As an adjunct to opioid
      Opioid
      An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...

       analgesia, such as the product Twilight Sleep
      Twilight sleep
      Twilight sleep is an amnesic condition characterized by insensibility to pain without loss of consciousness, induced by an injection of morphine and scopolamine, especially to relieve the pain of childbirth...

       which contained morphine
      Morphine
      Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...

       and scopolamine, some of the original formulations of Percodan
      Percodan
      Percodan is a drug marketed by Endo Pharmaceuticals. It is a tablet containing a mixture of 325 mg of aspirin and 4.8355 mg of oxycodone HCl . It is used to treat moderate to severe pain...

       and some European brands of methadone
      Methadone
      Methadone is a synthetic opioid, used medically as an analgesic and a maintenance anti-addictive for use in patients with opioid dependency. It was developed in Germany in 1937...

       injection..
    • As an over-the-counter sedative
      Sedative
      A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....

      , (Up until November 1990 scopolamine in minute doses could be purchased OTC legally in the United States).

Nausea

Its use as an antiemetic
Antiemetic
An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer....

 in the form of a transdermal patch
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. Often, this promotes healing to an injured area of the body. An advantage of a transdermal drug delivery route over other types of...

 (applied behind the external ear).

Ophthalmic

The drug is used in eye drops to induce mydriasis
Mydriasis
Mydriasis is a dilation of the pupil due to disease, trauma or the use of drugs. Normally, the pupil dilates in the dark and constricts in the light to respectively improve vividity at night and to protect the retina from sunlight damage during the day...

 (pupillary dilation) and cycloplegia
Cycloplegia
Cycloplegia is paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation.-Anatomy:The iris is the heavily pigmented colored part of the eye. It has a contractile diaphragm in front of the lens with a central opening called the pupil...

 (paralysis of the eye focusing muscle), primarily in the treatment of eye disorders that benefit from its prolonged effect, e.g. uveitis
Uveitis
Uveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....

, iritis
Iritis
Iritis is a form of anterior uveitis and refers to the inflammation of the iris of the eye.-Types:There are two main types of iritis: acute and chronic. They differ in numerous ways....

, iridocyclitis
Iridocyclitis
Iridocyclitis, a type of anterior uveitis, is a condition in which the uvea of the eye is inflamed.Iridocyclitis isInflammation of the iris and the ciliary body.- Symptoms :Symptoms include:* Photophobia* Redness* Watering of the eyes* Lacrimation...

, etc.

Memory research

Because of its anticholinergic effects, scopolamine has been shown to prevent the activation of medial temporal lobe structures for novel stimuli during spatial memory
Spatial memory
In cognitive psychology and neuroscience, spatial memory is the part of memory responsible for recording information about one's environment and its spatial orientation. For example, a person's spatial memory is required in order to navigate around a familiar city, just as a rat's spatial memory is...

 tasks. It has also been shown to impair memory in humans to mimic the cognitive deficits found in Alzheimer's Dementia.

Addiction

Scopolamine has been used in the past to treat addiction to drugs such as heroin and cocaine. The patient was given frequent doses of scopolamine until they were delirious. This treatment was maintained for 2 to 3 days after which they were treated with pilocarpine
Pilocarpine
Pilocarpine is a parasympathomimetic alkaloid obtained from the leaves of tropical American shrubs from the genus Pilocarpus. It is a non-selective muscarinic receptor agonist in the parasympathetic nervous system, which acts therapeutically at the muscarinic acetylcholine receptor M3 due to its...

. After recovering from this they were said to have lost the acute craving to the drug to which they were addicted.

Currently, scopolamine is being investigated for its possible usefulness alone or in conjunction with other drugs in treating nicotine
Nicotine
Nicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...

 addiction. The mechanism by which it mitigates withdrawal symptoms is different from that of clonidine
Clonidine
Clonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...

 meaning that the two drugs can be used together without duplicating or canceling out the effects of each other.

Other medical uses

  • It can be used as a depressant of the central nervous system
    Central nervous system
    The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

    , and was formerly used as a bedtime sedative.
  • Anesthetic; Its use in general anesthesia is favored by some due to its amnesic effect. Scopolamine causes memory impairments to a similar degree as diazepam
    Diazepam
    Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...

    .
  • In otolaryngology
    Otolaryngology
    Otolaryngology or ENT is the branch of medicine and surgery that specializes in the diagnosis and treatment of ear, nose, throat, and head and neck disorders....

     it is used to dry the upper airway (anti-sialogogue action) prior to instrumentation of the airway.
  • In October 2006 researchers at the US National Institute of Mental Health
    National Institute of Mental Health
    The National Institute of Mental Health is one of 27 institutes and centers that make up the National Institutes of Health...

     found that scopolamine reduced symptoms of depression
    Depression (mood)
    Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

     within a few days, and the improvement lasted for at least a week after switching to a placebo
    Placebo
    A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...

    .
  • Intravenously administered scopolamine has been found to be effective against major depressive disorder. A phase II clinical trial of its efficacy against both major depressive disorder and depression due to bipolar disorder
    Bipolar disorder
    Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...

     when administered via transdermal patch
    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. Often, this promotes healing to an injured area of the body. An advantage of a transdermal drug delivery route over other types of...

    es is scheduled to finish in September 2011.
  • Due to its effectiveness against sea-sickness
    Sea-sickness
    Seasickness is a form of motion sickness characterized by a feeling of nausea and, in extreme cases, vertigo, experienced after spending time on a craft on water. It is typically brought on by the rocking motion of the craft. Some people are particularly vulnerable to the condition with minor...

     it has become commonly used by scuba
    Scuba set
    A scuba set is an independent breathing set that provides a scuba diver with the breathing gas necessary to breathe underwater during scuba diving. It is much used for sport diving and some sorts of work diving....

     divers.
  • In Colombia
    Colombia
    Colombia, officially the Republic of Colombia , is a unitary constitutional republic comprising thirty-two departments. The country is located in northwestern South America, bordered to the east by Venezuela and Brazil; to the south by Ecuador and Peru; to the north by the Caribbean Sea; to the...

     a plant admixture containing scopolamine called Burundanga has been used shamanically
    Shamanism
    Shamanism is an anthropological term referencing a range of beliefs and practices regarding communication with the spiritual world. To quote Eliade: "A first definition of this complex phenomenon, and perhaps the least hazardous, will be: shamanism = technique of ecstasy." Shamanism encompasses the...

     for decades.
  • Scopolamine has been tested as a topical treatment for Aquagenic pruritus
    Aquagenic pruritus
    Aquagenic pruritus is a skin disease characterized by the development of severe, intense, prickling-like epidermal itching that is without observable skin lesions and that is evoked by contact with water.-Presentation:...

     and was shown in several cases to be effective.

Adverse effects

The common side effects are related to the anticholinergic effect on parasympathetic postsynaptic receptors: dry mouth, throat and nasal passages in overdose cases progressing to impaired speech, thirst, blurred vision and sensitivity to light, constipation
Constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...

, difficulty urinating and tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

. Other effects of overdose include flushing and fever, as well as excitement, restlessness, hallucinations, or delirium
Delirium
Delirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...

. These side effects are commonly observed with oral or parenteral uses of the drug and generally not with topical ophthalmic use.

Use in scuba diving to prevent sea sickness has led to the discovery of another side effect
Adverse effect (medicine)
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...

. In deep water, below 50–60 feet, some divers have reported pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...

 in the eyes that subsides quickly if the diver ascends to a depth of 40 feet or less. Mydriatics can precipitate an attack of glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...

 in susceptible patients, so the medication should be used with extra caution among divers who intend to go below 50 feet.

Drug interactions

When combined with morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...

, scopolamine is useful for pre-medication for surgery or diagnostic procedures and was widely used in obstetrics in the past; the mixture also produces amnesia
Amnesia
Amnesia is a condition in which one's memory is lost. The causes of amnesia have traditionally been divided into categories. Memory appears to be stored in several parts of the limbic system of the brain, and any condition that interferes with the function of this system can cause amnesia...

 and a tranquillised state known as Twilight Sleep
Twilight sleep
Twilight sleep is an amnesic condition characterized by insensibility to pain without loss of consciousness, induced by an injection of morphine and scopolamine, especially to relieve the pain of childbirth...

, also the name of a proprietary drug available in the past in ampoules of injectable fluid containing morphine sulfate and scopolamine hydrobromide (and in some cases the phenothiazine anti-nauseants prochlorperazine or promethazine as a third ingredient). Although originally used in obstetrics
Obstetrics
Obstetrics is the medical specialty dealing with the care of all women's reproductive tracts and their children during pregnancy , childbirth and the postnatal period...

, it is now considered dangerous for that purpose for both mother and baby.

Recreational use

The use of medical scopolamine/opioid combination preparations for euphoria is uncommon but does exist and can be seen in conjunction with opioid use. Doses of scopolamine by itself near the therapeutic range create euphoria and anxiolysis
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...

 of anticholinergic origin, similar to that of some first-generation antihistamines and similar drugs.

Another separate group of users prefer dangerously high doses, especially in the form of datura
Datura
Datura is a genus of nine species of vespertine flowering plants belonging to the family Solanaceae. Its precise and natural distribution is uncertain, owing to its extensive cultivation and naturalization throughout the temperate and tropical regions of the globe...

 preparations, for the deliriant and hallucinogenic effects. The hallucinations produced by scopolamine, in common with other potent anticholinergics, are especially real-seeming, with many users reporting hallucinations such as spiders crawling on walls and ceilings, especially in the dark. While some users find this pleasant, often the experience is not one that the user would want to repeat. An overdose of scopolamine is also exceedingly unpleasant physically, and can be fatal, unlike the effect of other more commonly used hallucinogens. For these reasons, naturally occurring anticholinergics are rarely used for recreational purposes.

Scopolamine in transdermal, oral, sublingual, and injectable formulations can produce a cholinergic rebound effect
Rebound effect
The rebound effect, or rebound phenomenon, is the tendency of some medications, when discontinued suddenly, to cause a return of the symptoms it relieved, and that, to a degree stronger than they were before treatment first began...

 when high doses are stopped. This is the opposite of scopolamine's therapeutic effects: sweating, runny nose, abdominal cramps, nausea, vomiting, vertigo, dizziness, irritability, and diarrhea. Psychological dependence is also possible when the drug is taken for its tranquilizing effects.

Use in interrogation

The effects of scopolamine were studied by criminologists in the early 20th century. However, scopolamine as a truth drug
Truth drug
A truth drug or truth serum is a psychoactive medication used to obtain information from subjects who are unable or unwilling to provide it otherwise. The unethical use of truth drugs is classified as a form of torture according to international law. However, they are properly and productively...

 was not seriously tested for this purpose until the 1950s when it was experimented on by various intelligence agencies, including the CIA as part of Project MKULTRA
Project MKULTRA
Project MKULTRA, or MK-ULTRA, was the code name for a covert, illegal CIA human experimentation program, run by the CIA's Office of Scientific Intelligence. This official U.S. government program began in the early 1950s, continued at least through the late 1960s, and used U.S...

. In 2009, it was proven that Czechoslovak
Czechoslovakia
Czechoslovakia or Czecho-Slovakia was a sovereign state in Central Europe which existed from October 1918, when it declared its independence from the Austro-Hungarian Empire, until 1992...

 communist
Communism
Communism is a social, political and economic ideology that aims at the establishment of a classless, moneyless, revolutionary and stateless socialist society structured upon common ownership of the means of production...

 secret police
STB
STB is an acronym that can mean:* Sacrae Theologiae Baccalaureus – Bachelor of Sacred Theology* Set-top box – a television device that converts signals to viewable images* Simpson Thacher & Bartlett LLP -- a law firm...

 used scopolamine at least three times to obtain confessions from alleged anti-state conspirators.

Criminal use and urban legends

In 1910 it was detected in the remains believed to be those of Cora Crippen, wife of Dr. Hawley Harvey Crippen
Hawley Harvey Crippen
Hawley Harvey Crippen , usually known as Dr. Crippen, was an American homeopathic physician hanged in Pentonville Prison, London, on November 23, 1910, for the murder of his wife, Cora Henrietta Crippen...

, and was accepted at the time as the cause of her death since her husband was known to have bought some at the start of the year. Scopolamine poisoning is sometimes reported by the media as method by which people are raped, killed, or robbed, although largely exaggerated in many unfounded rumors.

For example, there have been a number of unfounded circulating rumors that robbers in the United States used a transcutaneous
Transdermal
Transdermal is a route of administration wherein active ingredients are delivered across the skin for systemic distribution. Examples include transdermal patches used for medicine delivery, and transdermal implants used for medical or aesthetic purposes....

 delivery mechanism involving business cards, pamphlet
Pamphlet
A pamphlet is an unbound booklet . It may consist of a single sheet of paper that is printed on both sides and folded in half, in thirds, or in fourths , or it may consist of a few pages that are folded in half and saddle stapled at the crease to make a simple book...

s or flyer
Flyer (pamphlet)
__notoc__A flyer or flier, also called a circular, handbill or leaflet, is a form of paper advertisement intended for wide distribution and typically posted or distributed in public place....

s laced with the drug. However, in actual fact, the quantity of toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...

 diffusing through the skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...

 barrier after one short contact of the fingers with an object is much too small to be readily absorbed in the body and to have any significant effect. The use of burundanga (aka scopolamine) impregnated credit cards to attack and to rob isolated people is often propagated by chain emails and is presently reported as hoax
Hoax
A hoax is a deliberately fabricated falsehood made to masquerade as truth. It is distinguishable from errors in observation or judgment, or rumors, urban legends, pseudosciences or April Fools' Day events that are passed along in good faith by believers or as jokes.-Definition:The British...

 or urban legend
Urban legend
An urban legend, urban myth, urban tale, or contemporary legend, is a form of modern folklore consisting of stories that may or may not have been believed by their tellers to be true...

 by many specialized web sites.

Nevertheless, approximately one in five emergency room admissions for poisoning in Bogotá
Bogotá
Bogotá, Distrito Capital , from 1991 to 2000 called Santa Fé de Bogotá, is the capital, and largest city, of Colombia. It is also designated by the national constitution as the capital of the department of Cundinamarca, even though the city of Bogotá now comprises an independent Capital district...

 have been attributed to scopolamine. In June 2008, more than 20 people were hospitalized with psychosis in Norway
Norway
Norway , officially the Kingdom of Norway, is a Nordic unitary constitutional monarchy whose territory comprises the western portion of the Scandinavian Peninsula, Jan Mayen, and the Arctic archipelago of Svalbard and Bouvet Island. Norway has a total area of and a population of about 4.9 million...

 after ingesting counterfeit Rohypnol tablets containing scopolamine.

There have also been reports of tourists being robbed after having scopolamine slipped into their food or drink. Recently, these incidents have been reported in Thailand.

Witchcraft and sorcery

Scopolamine was one of the active principles in many of the "flying ointment
Flying ointment
Flying ointment, also known as witches' flying ointment, green ointment, magic salve and lycanthropic ointment, is a hallucinogenic ointment said to be used by witches in the Early Modern period .- Composition :The ointment contains a fatty base and various herbal extracts, usually including...

s" used by witches, sorcerers and fellow travellers of many countries and cultures from millennia ago ostensibly down to the late 19th century or even to the present day. Scopolamine and related tropanes contributed both to the flying sensations and hallucinations sought by users of these compounds. Potions, solids of various types, and other forms were also used in some cases.

These ointments could contain any number of ingredients with belladonna, henbane, and other plants of the belladonna and datura families being present almost invariably; they were applied to large areas of the skin with the objective being to see the Gods or spirits, and/or be transported to the Sabbat.

The hallucinations, sensation of flying, often a rapid increase in libido, and other characteristic effects of this practice are largely attributable to the CNS and peripheral effects of scopolamine and other active drugs present in the ointments such as atropine
Atropine
Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...

, hyoscyamine
Hyoscyamine
Hyoscyamine is a tropane alkaloid. It is a secondary metabolite found in certain plants of the Solanaceae family, including henbane , mandrake , jimsonweed , tomato and deadly nightshade...

, mandragorine, scopoline, solanine
Solanine
Solanine is a glycoalkaloid poison found in species of the nightshade family , such as the potato . It can occur naturally in any part of the plant, including the leaves, fruit, and tubers. Solanine has fungicidal and pesticidal properties, and it is one of the plant's natural defenses...

, optical isomers of scopolamine and other tropane alkaloids.

The inclusion of belladonna/datura type plants amongst the dozens of ingredients in the Haitian zombie
Zombie
Zombie is a term used to denote an animated corpse brought back to life by mystical means such as witchcraft. The term is often figuratively applied to describe a hypnotized person bereft of consciousness and self-awareness, yet ambulant and able to respond to surrounding stimuli...

 drug is thought by some authorities to be at least somewhat likely, although scopolamine-bearing plant matter is almost certainly not the main active ingredient, which has been theorised to possibly be Tetrodotoxin
Tetrodotoxin
Tetrodotoxin, also known as "tetrodox" and frequently abbreviated as TTX, sometimes colloquially referred to as "zombie powder" by those who practice Vodou, is a potent neurotoxin with no known antidote. There have been successful tests of a possible antidote in mice, but further tests must be...

 or a related substance.

In popular culture

  • The fictional use of scopolamine as a truth serum
    Truth Serum
    Truth Serum is an independent comic book series created, written and drawn by author Jon Adams.-Overview:Originally published as a mini comic in 2001 and given away for free, it appeared as a three-issue mini series published by Slave Labor Graphics in 2002...

     is featured in a number of works including The House on 92nd Street
    The House on 92nd Street
    The House on 92nd Street is a 1945 black-and-white spy film directed by Henry Hathaway. The film, shot mainly in New York City, was released shortly after the end of World War II. The House on 92nd Street was made with the full cooperation of the Federal Bureau of Investigation , and its head, J....

    , Farewell, My Lovely
    Farewell, My Lovely
    Farewell, My Lovely is a 1940 novel by Raymond Chandler, the second novel he wrote featuring Los Angeles private eye Philip Marlowe. It was adapted for the screen three times.-Plot summary:...

    , Where Eagles Dare
    Where Eagles Dare
    Where Eagles Dare is a 1968 World War II action-adventure spy film starring Richard Burton, Clint Eastwood and Mary Ure. It was directed by Brian G. Hutton and shot on location in Upper Austria and Bavaria....

     and The Guns of Navarone
    The Guns of Navarone (novel)
    The Guns of Navarone is a 1957 novel about World War II by Scottish thriller writer Alistair MacLean that was made into a critically acclaimed film in 1961...

    .
  • In 1957, scopolamine achieved a moderate level of notoriety via its mention in the film I Was a Teenage Werewolf
    I Was a Teenage Werewolf
    I Was a Teenage Werewolf is a 1957 horror film starring Michael Landon as a troubled teenager and Whit Bissell as the primary adult. It was co-written and produced by cult film producer Herman Cohen, and was one of the most successful films released by American International Pictures...

    , where Dr. Alfred Brandon uses it as part of his endeavor to regress the titular character to his "primitive roots." According to Dr. Liz Kingsley's film review site "And You Call Yourself a Scientist", Brandon's line "Prepare the scopolamine!" is "the only scientifically accurate line in the whole film."
  • In Fear and Loathing In Las Vegas by Hunter S. Thompson
    Hunter S. Thompson
    Hunter Stockton Thompson was an American journalist and author who wrote The Rum Diary , Fear and Loathing in Las Vegas and Fear and Loathing on the Campaign Trail '72 .He is credited as the creator of Gonzo journalism, a style of reporting where reporters involve themselves in the action to...

    , Dr. Gonzo
    Oscar Zeta Acosta
    Oscar Zeta Acosta was an American attorney, politician, minor novelist and Chicano Movement activist, perhaps best known for his friendship with the American author Hunter S. Thompson, who characterized him as his Samoan Attorney, Dr...

     mentions an incident in which he was given an entire datura root as a gift, ate the entire thing at once, and subsequently went blind, had to be taken back to his house in a wheelbarrow, and started making noises like a raccoon
    Raccoon
    Procyon is a genus of nocturnal mammals, comprising three species commonly known as raccoons, in the family Procyonidae. The most familiar species, the common raccoon , is often known simply as "the" raccoon, as the two other raccoon species in the genus are native only to the tropics and are...

    .
  • In Carlos Castaneda
    Carlos Castaneda
    Carlos Castaneda was a Peruvian-born American anthropologist and author....

    's series of books The Teachings of Don Juan: A Yaqui Way of Knowledge, the datura plant is the least favored shamanic, revelatory drug of the titular character, however Castaneda shows an affinity for it. The book explores, in depth, Castaneda's alleged experiences under the influence of the drug, as well as the alleged rites surrounding its use and preparation.
  • Scopolamine and "Twilight Sleep" were integral to the plot of The X-Files
    The X-Files
    The X-Files is an American science fiction television series and a part of The X-Files franchise, created by screenwriter Chris Carter. The program originally aired from to . The show was a hit for the Fox network, and its characters and slogans became popular culture touchstones in the 1990s...

     season four episode Unruhe
    Unruhe
    "Unruhe" is a 1996 episode of The X-Files television series. It was the fourth episode broadcast in the show's fourth season, and the first episode to air on Sunday night when the show was moved from Fridays to Sundays. "Unruhe" features a man who kidnaps women and lobotomizes them...

    . The drug was used as an interrogation tool during Episode 9 of NBC's Kidnapped
    Kidnapped (TV series)
    Kidnapped is an American television drama series from Sony Pictures Television which aired on NBC from September 20, 2006, to August 11, 2007...

    . It was also featured in "Smut", a December 2008 episode of Law & Order: Special Victims Unit
    Law & Order: Special Victims Unit
    Law & Order: Special Victims Unit is an American police procedural television drama series set in New York City, where it is also primarily produced...

    s tenth season, in which a rapist used scopolamine to prevent the women he raped from resisting him and from forming memories.
  • According to Janet Flanner (Genêt), in her 1972 book Paris was Yesterday (1925–1939), a collection of her New Yorker
    The New Yorker
    The New Yorker is an American magazine of reportage, commentary, criticism, essays, fiction, satire, cartoons and poetry published by Condé Nast...

    pieces, Prince Yussupoff was accused of poisoning with scopolamine the family of Princess Demidoff at regular tea parties, producing,

    on her noble family, and all their tea-drinking friends – a state of complete stupidity which none of these aristocrats found strange. Memory vanished, general conversation lagged, the two children dropped behind in their studies and became unable to add two and two without exciting comment from their proud parents. Casual guests popping in for a le five-o'clock were led back to their limousines in a state of complete imbecility; and an aunt, the Duchesse de Luynes, fell flat on her face after having sipped a cup of weak Orange Pekoe ('which was abnormal for Her Grace').

External links

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