Scopolamine

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(Redirected from
Hyoscine hydrobromide
)

Scopolamine
Clinical data
Trade namesTransdermscop, Kwells, others
Other namesHyoscine[1]
AHFS/Drugs.comMonograph
MedlinePlusa682509
License data
Pregnancy
category
  • AU: B2
intramuscular
Drug class
ATC code
Legal status
Legal status
Pharmacokinetic data
MetabolismLiver
Elimination half-life4.5 hours[6]
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
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)

Scopolamine, also known as hyoscine,[7] or Devil's Breath,[8] is a natural or synthetically produced tropane alkaloid and anticholinergic drug that is used as a medication to treat motion sickness[9] and postoperative nausea and vomiting.[10][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 orally and as a transdermal patch since it has been long known to have transdermal bioavailability.[1][11]

Scopolamine is in the

antimuscarinic family of drugs and works by blocking some of the effects of acetylcholine within the nervous system.[1]
Scopolamine was first written about in 1881 and started to be used for

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:[20][21]

It is sometimes used as a

dilated pupils, and dry mouth.[1] It is not recommended in people with angle-closure glaucoma or bowel obstruction.[1] Whether its use during pregnancy is safe remains unclear, and use during breastfeeding is still cautioned by health professionals and manufacturers of the drug.[27]

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.[27]

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.[28][29]

Adverse effects

Adverse effect incidence:[5][30][31][32]

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

  • Dry mouth
  • Anhidrosis (reduced ability to sweat to cool off)
  • Tachycardia (usually occurs at higher doses and is succeeded by bradycardia)
  • Bradycardia
  • Urticaria
    (hives)
  • Pruritus
    (itching)

Rare (<0.1% incidence) adverse effects include:

Unknown frequency adverse effects include:

Overdose

emesis (vomiting) are usually recommended as treatments for oral overdoses.[32] The symptoms of overdose include:[31][32]

Interactions

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

benzodiazepines, buprenorphine, and especially anticholinergic drugs such as tiotropium, diphenhydramine, dimenhydrinate, etc. Nicotine in particular likely has a counteracting effect on the effects of scopolamine due to its opposing effect on acetylcholine signaling.[citation needed
]

Route of administration

Scopolamine can be taken

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.[35]

Pharmacodynamics

The pharmacological effects of scopolamine are mediated through the drug's competitive antagonism of the peripheral and central muscarinic acetylcholine receptors. Scopolamine acts as a nonspecific muscarinic antagonist at all four (M1, M2, M3, and M4) receptor sites.[36][37]

In doses higher than intended for medicinal use; the hallucinogenic

alteration of consciousness, as well as the deliriousness in particular are tied to the compound's activity at the M1 muscarinic receptor. M1 receptors are located primarily in the central nervous system and are involved in perception, attention and cognitive functioning. Delirium is only associated with the antagonism of postsynaptic M1 receptors and currently other receptor subtypes have not been implicated.[38] Peripheral muscarinic receptors are part of the autonomic nervous system. M2 receptors are located in the brain and heart, M3 receptors are in salivary glands and M4 receptors are in the brain and lungs.[38] Due to the drug's inhibition of various signal transduction pathways, the decrease in acetylcholine signaling is what leads to many of the cognitive deficits, mental impairments and delirium associated with psychoactive doses. Medicinal effects appear to mostly be tied to activation of the peripheral receptors and only from marginal decreases in acetylcholine signaling.[39]

Although often broadly referred to as simply being 'anticholinergic',

Biosynthesis in plants

Scopolamine is among the

Biochemistry of tropane class compounds. Hyoscyamine and scopolamine are present and labeled.

The

L-ornithine to putrescine by ornithine decarboxylase. Putrescine is methylated to N-methylputrescine by putrescine N-methyltransferase.[41]

A

enzymatic activity could be demonstrated to catalyze this reaction. Hygrine further rearranges to tropinone.[41]

Subsequently,

History

Plants naturally containing scopolamine such as

New and Old Worlds since ancient times.[43][44][45] 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,[46] 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 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.[citation needed
]

In 1899, a Dr. Schneiderlin recommended the use of scopolamine and morphine for surgical anaesthesia, and it started to be used sporadically for that purpose.[12][47] 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, Germany, starting in 1903.[48] The method, which was based on a drug synergy between both scopolamine and morphine came to be known as Dämmerschlaf ("twilight sleep") or the "Freiburg method".[47][48] It spread rather slowly, and different clinics experimented with different dosages and ingredients; in 1915, the Canadian Medical Association Journal reported, "the method [was] really still in a state of development".[47] It remained widely used in the US until the 1960s, when growing chemophobia and a desire for more natural childbirth led to its abandonment.[49]

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.[15][50]

Australian bush medicine

A

Invasion of Normandy. 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 based on this substance.[51]

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

synergistic, but even more toxic mixture of the additional alkaloids in the plants which includes atropine and hyoscyamine
.

Historically, the various plants that produce scopolamine have been used psychoactively for

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.[60]

In Christianity, although not explicitly designated for

ritualistic or spiritual use; in the Bible there are multiple mentions of Mandrake 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, who apparently was "barren" (infertile) but trying to conceive.[61][62]

Interrogation

The effects of scopolamine were studied for use as a truth serum in interrogations in the early 20th century,[63] but because of the side effects, investigations were dropped.[64] In 2009, the Czechoslovak state security secret police were proven to have used scopolamine at least three times to obtain confessions from alleged antistate dissidents.[65]

Crime in Colombia

A travel advisory published by the US Overseas Security Advisory Council (OSAC) 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 scopolamine. Unofficial estimates put the number of annual scopolamine incidents in Colombia at approximately 50,000. Scopolamine 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 scopolamine, 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 scopolamine or other drugs should seek immediate medical attention.[66]

Between 1998 and 2004, 13% of emergency-room admissions for "poisoning with criminal intentions" in a clinic of Bogotá, Colombia, have been attributed to scopolamine, and 44% to benzodiazepines.[15] 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.[15]

Beside robberies, it is also allegedly involved in

alcohol poisoning.[81][82]

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.

memory retention and free recall compared to DPH (an anticholinergic and antihistamine).[82]

Scopolamine produces detrimental effects on short-term memory, memory acquisition, learning, visual recognition memory,

Alzheimer's, dementia, fragile X syndrome, and Down syndrome.[85][89][90][91]

Scopolamine has been identified as a psychoplastogen, which refers to a compound capable of promoting rapid and sustained neuroplasticity in a single dose.[92] It has been, and continues to be investigated as a rapid-onset antidepressant, with a number of small studies finding positive results, particularly in female subjects.[93][94][95][96]

NASA 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.[97]

Although a fair amount of research has been applied to scopolamine in the field of medicine, its

disassociative compounds, despite the alkaloid's long history of usage in mind-altering plant preparations.[98]

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External links

  • Media related to Scopolamine at Wikimedia Commons
  • "Scopolamine". Drug Information Portal. U.S. National Library of Medicine.