|Trade names||Transdermscop, Kwells, others|
|Other names||Scopolamine, hyoscinehydrobromide, scopolamine hydrobromide|
|by mouth, skin patch, eye drops, subcutaneous, intravenous, sublingual, rectal, buccal transmucousal, intramuscular|
|Elimination half-life||4.5 hours|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||303.353 g/mol g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Hyoscine, also known as scopolamine, is a medication used to treat motion sickness and postoperative nausea and vomiting. It is also sometimes used before surgery to decrease saliva. When used by injection, effects begin after about 20 minutes and last for up to 8 hours. It may also be used by mouth and as a skin patch.
Common side effects include sleepiness, blurred vision, dilated pupils, and dry mouth. It is not recommended in people with angle-closure glaucoma or bowel obstruction. It is unclear if use during pregnancy is safe; however, it appears to be safe during breastfeeding. Hyoscine is in the antimuscarinic family of medications and works by blocking some of the effects of acetylcholine within the nervous system.
Hyoscine was first written about in 1881 and started to be used for anesthesia around 1900. It is on the WHO Model List of Essential Medicines, the most effective and safe medicines needed in a health system. Hyoscine is produced by plants of the nightshade family which historically have been used as psychoactive drugs. The name "scopolamine" is derived from one type of nightshade known as Scopolia while the name "hyoscine" is derived from another type known as Hyoscyamus niger.
- 1 Medical use
- 2 Adverse effects
- 3 Overdose
- 4 Interactions
- 5 Route of administration
- 6 Pharmacodynamics
- 7 Biosynthesis in plants
- 8 History
- 9 Society and culture
- 10 Research
- 11 See also
- 12 References
- 13 External links
- Postoperative nausea and vomiting and sea sickness, leading to its use by scuba divers
- Motion sickness (where it is often applied as a transdermal patch behind the ear)
- Gastrointestinal spasms
- Renal or biliary spasms
- Aid in gastrointestinal radiology and endoscopy
- Irritable bowel syndrome
- Clozapine-induced hypersalivation (drooling)
- Bowel colic
- Eye inflammation
Hyoscine crosses the placenta and is a United States pregnancy category C and Australian Category B1 medication, meaning a risk to the fetus cannot be ruled out. Sufficient studies in women and animals are not available to rule out harm, but existing studies have not shown increased risk. Drugs should be given only if the potential benefits justify the potential risk to the fetus. It may cause respiratory depression and/or neonatal hemorrhage when used during pregnancy. Transdermal hyoscine has been used as an adjunct to epidural anesthesia for Caesarean delivery without adverse CNS effects on the newborn. Except when used prior to Caesarean section, it should only be used during pregnancy if the benefit to the mother outweighs the potential risk to the fetus.
Hyoscine enters breast milk by secretion. Although no human studies exist to document the safety of hyoscine while nursing, the manufacturer recommends that caution be taken if hyoscine is administered to a breastfeeding woman.
The likelihood of experiencing adverse effects from hyoscine is increased in the elderly relative to younger people. This phenomenon is especially true for older people who are also on several other medications. It is recommended that hyoscine 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.
Uncommon (0.1–1% incidence) adverse effects include:
- Dry mouth
- Dyshidrosis (reduced ability to sweat in order to cool off)
- Tachycardia (usually occurs at higher doses and is succeeded by bradycardia)
- Urticaria (hives)
- Pruritus (itching)
Rare (<0.1% incidence) adverse effects include:
Unknown frequency adverse effects include:
- Anaphylactic shock
- Anaphylactic reactions
- Dyspnea (shortness of breath)
- Other hypersensitivity reactions
- Blurred vision
- Mydriasis (dilated pupils)
Physostigmine is a cholinergic drug that readily crosses the blood-brain barrier, and has been used as an antidote to treat the central nervous system depression symptoms of a hyoscine overdose. Other than this supportive treatment, gastric lavage and induced emesis (vomiting) are usually recommended as treatments for oral overdoses. The symptoms of overdose include:
- Blurred vision
- Urinary retention
- Drowsiness or paradoxical reaction which can present with hallucinations
- Cheyne-Stokes respiration
- Dry mouth
- Skin reddening
- Inhibition of gastrointestinal motility
Due to interactions with metabolism of other drugs, hyoscine can cause significant unwanted side effects when taken with other medications. Specific attention should be paid to other medications in the same pharmacologic class as hyoscine, also known as anticholinergics. The following medications could potentially interact with the metabolism of hyoscine: analgesics/pain medications, ethanol, zolpidem, thiazide diuretics, buprenorphine, anticholinergic drugs such as tiotropium, etc.
Route of administration
Hyoscine can be taken by mouth, subcutaneously, ophthalmically and intravenously, as well as via a transdermal patch. The transdermal patch (e.g., Transderm Scōp) for prevention of nausea and motion sickness employs hyoscine base, and is effective for up to three days. The oral, ophthalmic, and intravenous forms have shorter half-lives and are usually found in the form hyoscine hydrobromide (for example in Scopace, soluble tablets or Donnatal).
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Biosynthesis in plants
Hyoscine is among the secondary metabolites of plants from Solanaceae (nightshade) family of plants, such as henbane, jimson weed (Datura), angel's trumpets (Brugmansia), and corkwood (Duboisia).
The biosynthesis of hyoscine begins with the decarboxylation of L-ornithine to putrescine by ornithine decarboxylase. Putrescine is methylated to N-methylputrescine by putrescine N-methyltransferase.
A putrescine oxidase that specifically recognizes methylated putrescine catalyzes the deamination of this compound to 4-methylaminobutanal, which then undergoes a spontaneous ring formation to N-methyl-pyrrolium cation. In the next step, the pyrrolium cation condenses with acetoacetic acid yielding hygrine. No enzymatic activity could be demonstrated to catalyze this reaction. Hygrine further rearranges to tropinone.
Subsequently, tropinone reductase I converts tropinone to tropine which condenses with phenylalanine-derived phenyllactate to littorine. A cytochrome P450 classified as Cyp80F1 oxidizes and rearranges littorine to hyoscyamine aldehyde. In the final step, hyoscyamine undergoes epoxidation catalyzed by 6beta-hydroxyhyoscyamine epoxidase yielding hyoscine.
One of the earlier alkaloids isolated from plant sources, hyoscine 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 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 hyoscine by Ladenburg, the search for synthetic analogues of and methods for total synthesis of hyoscine and/or atropine in the 1930s and 1940s resulted in the discovery of diphenhydramine, an early antihistamine and the prototype of its chemical subclass of these drugs, and pethidine, the first fully synthetic opioid analgesic, known as Dolantin and Demerol amongst many other trade names.
In 1899, a Dr. Schneiderlin recommended the use of hyoscine and morphine for surgical anaesthesia and it started to be used sporadically for that purpose. The use of this combination in obstetric anesthesiology, was first proposed by Richard von Steinbuchel in 1902 then was picked up and further developed by Carl Gauss in Freiburg, Germany starting in 1903. The method came to be known as "Dämmerschlaf" ("twilight sleep") 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 that "the method [was] really still in a state of development". It remained widely used in the US until the 1960s, when growing chemophobia and a desire for more natural childbirth led to its abandonment.
Society and culture
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, so repeated use is rare. In June 2008, more than 20 people were hospitalized with psychosis in Norway after ingesting counterfeit Rohypnol tablets containing hyoscine. In January 2018, 9 individuals were hospitalized in Perth, Western Australia, after reportedly ingesting hyoscine.
Historically, the various plants which produce hyoscine have been used psychoactively for spiritual reasons. When entheogenic preparations of these plants were utilized, hyoscine 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). Hyoscine 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 at least as far back as the Early Modern period and included multiple ingredients to help with the transdermal absorption of hyoscine (such as animal fat) as well as other possible ingredients to counteract its noxious and dysphoric effects.
The effects of hyoscine were studied for use as a truth serum in interrogations in the early 20th century, but because of the side effects, investigations were dropped. In 2009, the Czechoslovak state security secret police were proven to have used hyoscine at least three times to obtain confessions from alleged antistate dissidents.
In 1910, hyoscine was detected in the remains believed to be those of Cora Crippen, wife of Dr. Hawley Harvey 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.
Claims that hyoscine is commonly used in crime have been described as "exaggerated" or even implausible. Powdered hyoscine, in a form referred to as 'Devil's breath' does not 'brainwash' or control people into being defrauded by their attackers but these alleged effects are most likely urban legends. Nevertheless, the drug is known to produce loss of memory following exposure and sleepiness, similar to the effect of benzodiazepines or alcohol poisoning.
A travel advisory published by the United States Department of State in 2012 stated: "One common and particularly dangerous method that criminals use in order to rob a victim is through the use of drugs. The most common [in Colombia] has been hyoscine. Unofficial estimates put the number of annual hyoscine incidents in Colombia at approximately 50,000. Hyoscine can render a victim unconscious for 24 hours or more. In large doses, it can cause respiratory failure and death. It is most often administered in liquid or powder form in foods and beverages. The majority of these incidents occur in night clubs and bars, and usually men, perceived to be wealthy, are targeted by young, attractive women. It is recommended that, to avoid becoming a victim of hyoscine, a person should never accept food or beverages offered by strangers or new acquaintances, nor leave food or beverages unattended in their presence. Victims of hyoscine or other drugs should seek immediate medical attention."
Beside robberies it is also allegedly involved in express kidnappings and sexual assault. The Hospital Clínic in Barcelona introduced a protocol 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 hyoscine 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. Hyoscine transdermal patches must be used for hours to days.
Between 1998 and 2004, 13% of emergency room admissions for poisoning with criminal intentions in a clinic of Bogotá, Colombia, have been attributed to hyoscine, 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. A Turkish-Canadian Professor, Ramazan Gençay, who was in the Department of Economics at Simon Fraser University was found dead in Colombia on 24 December 2018, with questions of if he was poisoned by hyoscine.
In 2019, a man was charged with murder after two men in London were found to have been poisoned with hyoscine. One of the men, Adrian Murphy, died.
Hyoscine 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 acetylcholine is involved in the encoding of new information into long term memory.
Hyoscine produces detrimental effects on short-term memory, memory acquisition, learning, visual recognition memory, visuospatial praxis, visuospatial memory, visuoperceptual function, verbal recall and psychomotor speed. However, scopolamine does not seem to impair recognition and memory retrieval. Acetylcholine projections in hippocampal neurons, which are vital mediating in mediating long term potentiation, are inhibited by scopolamine. Hyoscine also inhibits cholinergic mediated glutamate release in hippocampal neurons which assist in depolarization, potentiation of action potential, and synaptic suppression. Hyoscine's effects on acetylcholine and glutamate release in the hippocampus favors retrieval dominant cognitive functioning. Hyoscine has been used to model the defects in cholinergic function for models of Alzheimer’s, dementia, fragile X syndrome, and Down syndrome.
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