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Scopolamine

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For other uses, see Scopolamine (disambiguation).

Scopolamine
Clinical data
Trade namesTransdermscop, Kwells, others
Other namesScopolamine, hyoscinehydrobromide, scopolamine hydrobromide[1]
AHFS/Drugs.comMonograph
Pregnancy
category
  • AU: B2
Routes of
administration		by mouth, skin patch, eye drops, subcutaneous, intravenous, sublingual, rectal, buccal transmucousal, intramuscular
ATC code
Legal status
Legal status
Pharmacokinetic data
MetabolismLiver
Elimination half-life4.5 hours[2]
ExcretionKidney
Identifiers
  • (–)-(S)-3-Hydroxy-2-phenylpropionic acid (1R,2R,4S,5S,7α,9S)-9-methyl-3-oxa-9-azatricyclo[3.3.1.02,4]non-7-yl ester
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.083 Edit this at Wikidata
Chemical and physical data
FormulaC17H21NO4
Molar mass303.353 g/mol g·mol−1
3D model (JSmol)
  • OC[C@H](c1ccccc1)C(=O)O[C@@H]2C[C@H]3N(C)[C@@H](C2)[C@@H]4O[C@H]34
  • InChI=1S/C17H21NO4/c1-18-13-7-11(8-14(18)16-15(13)22-16)21-17(20)12(9-19)10-5-3-2-4-6-10/h2-6,11-16,19H,7-9H2,1H3/t11-,12-,13-,14+,15-,16+/m1/s1 checkY
  • Key:STECJAGHUSJQJN-FWXGHANASA-N checkY
 ☒NcheckY (what is this?)  (verify)

Hyoscine, also known as scopolamine,[3] is a medication used to treat motion sickness and postoperative nausea and vomiting.[1] It is also sometimes used before surgery to decrease saliva.[1] When used by injection, effects begin after about 20 minutes and last for up to 8 hours.[1] It may also be used by mouth and as a skin patch.[1]

Common side effects include sleepiness, blurred vision, dilated pupils, and dry mouth.[1] It is not recommended in people with glaucoma or bowel obstruction.[1] It is unclear if use during pregnancy is safe; however, it appears to be safe during breastfeeding.[4] Hyoscine is in the antimuscarinic family of medications and works by blocking some of the effects of acetylcholine within the nervous system.[1]

Hyoscine was first written about in 1881 and started to be used for anesthesia around 1900.[5][6] It is on the WHO Model List of Essential Medicines, the most effective and safe medicines needed in a health system.[7] Hyoscine is produced from plants of the nightshade family.[8] 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.[9][10]

Medical use

Hyoscine has a number of uses in medicine, where it is used to treat the following:[11][12]

It is sometimes used as a premedication (especially to reduce respiratory tract secretions) to surgery, mostly commonly by injection.[11][12]

Pregnancy

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.

Breastfeeding

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.[16]

Elderly

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.[17]

Adverse effects

Adverse effect incidence:[18][19][20][21]

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

Rare (<0.1% incidence) adverse effects include:

Unknown frequency adverse effects include:

Overdose

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.[22] Other than this supportive treatment, gastric lavage and induced emesis (vomiting) are usually recommended as treatments for oral overdoses.[21] The symptoms of overdose include:[20][21]

Interactions

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.[23] 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.[24] 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).

NASA is currently developing 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.[25]

Mechanism of action

Although it is usually referred to as a nonspecific antimuscarinic,[26] there is indirect evidence for m1-receptor subtype specificity.[27]

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).[28][9]

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.[29]

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.[29]

Subsequently, tropinone reductase I converts tropinone to tropine which condenses with phenylalanine-derived phenyllactate to littorine. A cytochrome P450 classified as Cyp80F1[30] oxidizes and rearranges littorine to hyoscyamine aldehyde. In the final step, hyoscyamine undergoes epoxidation catalyzed by 6beta-hydroxyhyoscyamine epoxidase yielding hyoscine.[29]

History

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,[31] 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 Dolatin 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 for purpose, sporadically.[5][32] 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.[33] The method came to be known as "Dämmerschlaf" ("twilight sleep") or the "Freiburg method".[32][33] 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".[32] It remained widely used in the US until the 1960s, when growing chemophobia and a desire for more natural childbirth led to its abandonment.[34]

Society and culture

Names

Hyoscine hydrobromide is the international nonproprietary name, and scopolamine hydrobromide is the United States Adopted Name. Other names include levo-duboisine, devil's breath and burundanga.[35]

Recreational 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.[36]

In June 2008, more than 20 people were hospitalized with psychosis in Norway after ingesting counterfeit Rohypnol tablets containing hyoscine.[37]

In January 2018, 9 individuals were hospitalised in Perth, Western Australia, after reportedly ingesting hyoscine.[38]

Interrogation

The effects of hyoscine were studied for use as a truth serum in interrogations in the early 20th century,[39] but because of the side effects, investigations were dropped.[40] In 2009, it was proven that the Czechoslovak state security secret police had used hyoscine at least three times to obtain confessions from alleged antistate dissidents.[41]

Crime

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.[42]

The drug is known to produce loss of memory following exposure and sleepiness, similar to the effect of benzodiazepines or alcohol poisoning, which affects the ability of a person to resist criminal aggression. 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. To avoid becoming a victim of hyoscine, one should never accept food or beverages offered by strangers or new acquaintances or leave food or beverages unattended. Victims of hyoscine or other drugs should seek immediate medical attention.[43]

Beside robberies it is also allegedly involved in express kidnappings and sexual assault.[44] The Hospital Clínic in Barcelona introduced a special protocol in 2008 to help medical workers identify cases, while Madrid hospitals adopted a similar working document in February 2015.[44] However, Hospital Clínic has found little scientific evidence to support this use and relies on the victims' stories to reach any conclusion.[44] 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 (added to drinks, transdermal injection, on playing cards and papers etc.) are often exaggerated,[45][46][47] especially the transdermal uses, as the dose that can be absorbed by the skin is too low to have any effect[44] (hyoscine transdermal patches must be used for hours to days).[23]

The name "burundanga" derives from being an extract of the brugmansia plant.[48]

About one in five emergency room admissions for poisoning in Bogotá, Colombia, have been attributed to hyoscine.[35] Most commonly, the victim 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.[35]

Research

Hyoscine has been used as a research tool to study the involvement of acetylcholine in cognition. Results in primates suggest that acetylcholine is involved in the encoding of new information into long term memory.[49] Hyoscine has also been investigated as a rapid-onset antidepressant with a number of small studies finding positive results.[50][51][52][53]

See also

References

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  5. ^ a b Keys, Thomas E. (1996). The history of surgical anesthesia (PDF) ([Reprint]. ed.). Park Ridge, Ill.: Wood Library, Museum of Anesthesiology. p. 48ff. ISBN 0-9614932-7-5.
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