Jump to content

Scopolamine

From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by GreenC bot (talk | contribs) at 21:16, 1 November 2022 (Remove 3 citations per WP:USURPURL and WP:JUDI. Wayback Medic 2.5). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

"Hyoscine" redirects here. For Other uses, see Hyoscine (disambiguation).
"Devil's Breath" redirects here. For the novel, see The Devil's Breath.

Scopolamine
Clinical data
Trade namesTransdermscop, Kwells, others
Other namesScopolamine, hyoscine hydrobromide, scopolamine hydrobromide[1]
AHFS/Drugs.comMonograph
MedlinePlusa682509
License data
Pregnancy
category
  • AU: B2
Routes of
administration		By mouth, transdermal, ophthalmic, subcutaneous, intravenous, sublingual, rectal, buccal, transmucosal, 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
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 mass303.358 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)

Scopolamine, also known as hyoscine,[7] or Devil's Breath,[8] is a natural or synthetically produced tropane alkaloid and anticholinergic drug that is formally used as a medication for treating motion sickness and postoperative nausea and vomiting.[9][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.[1]

Common side effects include sleepiness, blurred vision, 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.[10] 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 anesthesia around 1900.[11][12] Around this time it was first proposed for and then subsequently used for years to induce amnesia and synergistic pain relief during childbirth by administering a combination of both scopolamine and morphine.[13] These alkaloids when used in combination gave rise to a synergistic state called "twilight sleep".[14] Scopolamine is also the main active component produced by certain plants of the nightshade family, which historically have been used as psychoactive drugs (known as deliriants) due to their antimuscarinic-induced hallucinogenic effects.[9] 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.[15][16] It is on the World Health Organization's List of Essential Medicines.[17]

Medical uses

Scopolamine has a number of uses in medicine where it is used in low doses to treat:[18][19]

It is sometimes used as a premedication, (especially to reduce respiratory tract secretions) in surgery, most commonly by injection.[18][19]

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.[10]

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.[23][24]

Adverse effects

Adverse effect incidence:[5][25][26][27]

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

Rare (<0.1% incidence) adverse effects include:

Unknown frequency adverse effects include:

Overdose

Physostigmine, a cholinergic drug that readily crosses the blood-brain barrier, has been used as an antidote to treat the central nervous system depression symptoms of a scopolamine overdose.[28] Other than this supportive treatment, gastric lavage and induced emesis (vomiting) are usually recommended as treatments for oral overdoses.[27] The symptoms of overdose include:[26][27]

Interactions

Due to interactions with metabolism of other drugs, scopolamine can cause significant unwanted side effects or unpredictable synergies when taken with other medications or compounds. Specific attention should be paid to other medications in the same pharmacologic class as scopolamine, also known as anticholinergics. These additional compounds could also potentially interact with the metabolism of scopolamine: receptor-binding analgesic/pain medication such as gabapentinoids or opioids, ethanol, cannabinoids, zolpidem, thiazide diuretics, nicotine, benzodiazepines, buprenorphine, and especially anticholinergic drugs such as tiotropium, diphenhydramine, dimenhydrinate, etc.[citation needed]

Route of administration

Scopolamine can be taken by mouth, subcutaneously, in the eye, and intravenously, as well as via a transdermal patch.[29]

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.[30]

Pharmacodynamics

Scopolamine is a nonspecific muscarinic antagonist at all four muscarinic acetylcholine receptors (M1, M2, M3, and M4).,[31][32]

Biosynthesis in plants

Scopolamine is among the secondary metabolites of plants from Solanaceae (nightshade) family of plants, such as henbane (Hyoscyamus niger), jimson weed (Datura), angel's trumpets (Brugmansia), deadly nightshade (Belladonna), mandrake (Mandragora officinarum), and corkwood (Duboisia).[33][15]

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

The biosynthesis of scopolamine begins with the decarboxylation of L-ornithine to putrescine by ornithine decarboxylase. Putrescine is methylated to N-methylputrescine by putrescine N-methyltransferase.[34]

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.[34]

Subsequently, tropinone reductase I converts tropinone to tropine, which condenses with phenylalanine-derived phenyllactate to littorine. A cytochrome P450 classified as Cyp80F1[35] oxidizes and rearranges littorine to hyoscyamine aldehyde. In the final step, hyoscyamine undergoes epoxidation catalyzed by 6beta-hydroxyhyoscyamine epoxidase yielding scopolamine.[34]

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 in 1880,[36] 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.[11][14] The use of this combination in obstetric anesthesiology 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.[37] The method came to be known as Dämmerschlaf ("twilight sleep") or the "Freiburg method".[14][37] 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".[14] It remained widely used in the US until the 1960s, when growing chemophobia and a desire for more natural childbirth led to its abandonment.[38]

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.[39][40]

Australian bush medicine

A bush medicine developed by Aboriginal peoples of the eastern states of Australia from the soft corkwood tree (Duboisia myoporoides) was used by the Allies in World War II to stop soldiers from getting seasick when they sailed across the English Channel on their way to France during the 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.[41]

Recreational and religious use

While it has been occasionally used recreationally for its hallucinogenic properties, the experiences are often unpleasant, mentally and physically. It is also physically dangerous and officially classified as a deliriant drug, so repeated recreational use is rare.[42] In June 2008, more than 20 people were hospitalized with psychosis in Norway after ingesting counterfeit rohypnol tablets containing scopolamine.[43] In January 2018, 9 individuals were hospitalized in Perth, Western Australia, after reportedly ingesting scopolamine.[44] However, the alkaloid scopolamine, when taken recreationally for its psychoactive effect is usually taken in the form of preparations from plants of the genera Datura or Brugmansia, often by adolescents or young adults in order to achieve hallucinations and an altered state of consciousness induced by muscarinic antagonism.[45][46] In circumstances such as these, the intoxication is usually built on 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 spiritual and magical purposes.[47][48][49] When entheogenic preparations of these plants were used, scopolamine was considered to be the main psychoactive compound and was largely responsible for the hallucinogenic effects, particularly when the preparation was made into a topical ointment (most notably flying ointment).[50] Scopolamine is reported to be the only active alkaloid within these plants that can effectively be absorbed through the skin to cause effects.[51] 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 scopolamine (such as animal fat), as well as other possible ingredients to counteract its noxious and dysphoric effects.[50]

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.[52][53]

Interrogation

The effects of scopolamine were studied for use as a truth serum in interrogations in the early 20th century,[54] but because of the side effects, investigations were dropped.[55] 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.[56]

Crime

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.[57]

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.[39] 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.[39]

Beside robberies, it is also allegedly involved in express kidnappings and sexual assault.[58] 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.[58] Hospital Clínic has found little scientific evidence to support this use and relies on the victims' stories to reach any conclusion.[58] Although poisoning by scopolamine appears quite often in the media as an aid for raping, kidnapping, killing, or robbery, the effects of this drug and the way it is applied by criminals (transdermal injection, on playing cards and papers, etc.) are often exaggerated,[59][60][61] especially skin exposure, as the dose that can be absorbed by the skin is too low to have any effect.[58] Scopolamine transdermal patches must be used for hours to days.[29] There are certain other aspects of the usage of scopolamine in crimes. Powdered scopolamine is referred to as "devil's breath". In popular media and television, it is portrayed as a method to brainwash or control people into being defrauded by their attackers;[62][63][64][65] there is debate whether these claims are true.[66][67] It is not verified if the powdered form is capable of inducing a suggestive state. The danger is real enough that in addition to the Overseas Security Advisory Council (OSAC) in 2012, the US Department of State, as well as the Government of Canada, published [68][69] travel advisories warning travelers about the possibility of targeting. Criminals using Devil’s Breath often use attractive, young women to target men that they believe are wealthy.[70] Nevertheless, the drug is known to produce loss of memory following exposure and sleepiness, similar to the effect of benzodiazepines or alcohol poisoning.[71][72]

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.[73] Since then, scopolamine has become a standard drug for experimentally inducing cognitive defects in animals.[74][75] Results in primates suggest that acetylcholine is involved in the encoding of new information into long-term memory.[76]

Scopolamine produces detrimental effects on short-term memory, memory acquisition, learning, visual recognition memory, visuospatial praxis, visuospatial memory, visuoperceptual function, verbal recall, and psychomotor speed.[77][74][75] It does not seem to impair recognition and memory retrieval, though.[75] Acetylcholine projections in hippocampal neurons, which are vital in mediating long-term potentiation, are inhibited by scopolamine.[75][78] Scopolamine also inhibits cholinergic-mediated glutamate release in hippocampal neurons, which assist in depolarization, potentiation of action potential, and synaptic suppression. Scopolamine's effects on acetylcholine and glutamate release in the hippocampus favor retrieval-dominant cognitive functioning.[75] Scopolamine has been used to model the defects in cholinergic function for models of Alzheimer's, dementia, fragile X syndrome, and Down syndrome.[75][79][80][81]

Scopolamine has also been investigated as a rapid-onset antidepressant, with a number of small studies finding positive results.[82][83][84][85]

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.[86]

References

  1. ^ a b c d e f g h "Scopolamine". The American Society of Health-System Pharmacists. Archived from the original on 7 October 2016. Retrieved 8 December 2016.
  2. ^ "Poisons Standard October 2020". Federal Register of Legislation. 30 September 2020. Retrieved 23 October 2020.
  3. ^ "Hyoscine Hydrobromide 400 micrograms/ml Solution for Injection - Summary of Product Characteristics (SmPC)". (emc). Retrieved 23 October 2020.
  4. ^ "Kwells 300 microgram tablets - Summary of Product Characteristics (SmPC)". (emc). Retrieved 23 October 2020.
  5. ^ a b "Transderm Scop- scopolamine patch, extended release". DailyMed. Retrieved 4 February 2022.
  6. ^ Putcha L, Cintrón NM, Tsui J, Vanderploeg JM, Kramer WG (June 1989). "Pharmacokinetics and oral bioavailability of scopolamine in normal subjects". Pharmaceutical Research. 6 (6): 481–485. doi:10.1023/A:1015916423156. PMID 2762223. S2CID 27507555.
  7. ^ Juo PS (2001). Concise Dictionary of Biomedicine and Molecular Biology (2nd ed.). Hoboken: CRC Press. p. 570. ISBN 9781420041309. Archived from the original on 10 September 2017.
  8. ^ Duffy R (23 July 2007). "Colombian Devil's Breath". Vice. Retrieved 3 February 2022.
  9. ^ a b Osbourn AE, Lanzotti V (2009). Plant-derived Natural Products: Synthesis, Function, and Application. Springer Science & Business Media. p. 5. ISBN 9780387854984. Archived from the original on 10 September 2017.
  10. ^ a b Briggs GG, Freeman RK, Yaffe SJ (1994). "Scopolamine". Drugs in Pregnancy and Lactation. Baltimore, Maryland: Williams and Wilkins. pp. 777–778. ISBN 9780683010602.
  11. ^ a b Keys TE (1996). The history of surgical anesthesia (PDF) (Reprint ed.). Park Ridge, Ill.: Wood Library, Museum of Anesthesiology. p. 48ff. ISBN 978-0-9614932-7-1.
  12. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 551. ISBN 9783527607495.
  13. ^ Keys TE (1996). The history of surgical anesthesia (PDF) ([Reprint]. ed.). Park Ridge, Ill.: Wood Library, Museum of Anesthesiology. p. 48ff. ISBN 0-9614932-7-5.
  14. ^ a b c d "Twilight Sleep: the Dammerschlaf of the Germans". Canadian Medical Association Journal. 5 (9): 805–808. September 1915. PMC 1584452. PMID 20310688.
  15. ^ a b The Chambers Dictionary. Allied Publishers. 1998. pp. 788, 1480. ISBN 978-81-86062-25-8.
  16. ^ Cattell HW (1910). Lippincott's new medical dictionary: a vocabulary of the terms used in medicine, and the allied sciences, with their pronunciation, etymology, and signification, including much collateral information of a descriptive and encyclopedic character. Lippincott. p. 435. Archived from the original on 10 September 2017. Retrieved 25 February 2012.
  17. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  18. ^ a b Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. pp. 49, 266, 822, 823. ISBN 978-0-85711-084-8.
  19. ^ a b Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
  20. ^ Bitterman N, Eilender E, Melamed Y (May 1991). "Hyperbaric oxygen and scopolamine". Undersea Biomedical Research. 18 (3): 167–174. PMID 1853467. Archived from the original on 20 August 2008. Retrieved 13 August 2008.{{cite journal}}: CS1 maint: unfit URL (link)
  21. ^ Williams TH, Wilkinson AR, Davis FM, Frampton CM (March 1988). "Effects of transcutaneous scopolamine and depth on diver performance". Undersea Biomedical Research. 15 (2): 89–98. PMID 3363755. Archived from the original on 20 August 2008.{{cite journal}}: CS1 maint: unfit URL (link)
  22. ^ "scopolamine solution - ophthalmic, Isopto". MedicineNet.com. Retrieved 12 February 2019.
  23. ^ "Study suggests link between long-term use of anticholinergics and dementia risk". Alzheimer's Society. 26 January 2015. Archived from the original on 12 November 2015. Retrieved 17 February 2015.
  24. ^ Flicker C, Ferris SH, Serby M (1992). "Hypersensitivity to scopolamine in the elderly". Psychopharmacology. 107 (2–3): 437–441. doi:10.1007/bf02245172. PMID 1615141. S2CID 29065240.
  25. ^ "DBL HYOSCINE INJECTION BP". TGA eBusiness Services. Hospira Australia Pty Ltd. 30 January 2012. Archived from the original on 30 March 2017. Retrieved 22 October 2013.
  26. ^ a b "Buscopan Tablets - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Boehringer Ingelheim Limited. 11 September 2013. Archived from the original on 23 October 2013. Retrieved 22 October 2013.
  27. ^ a b c "Kwells 300 microgram tablets - Summary of Product Characteristics". electronic Medicines Compendium. Bayer plc. 7 January 2008. Archived from the original on 23 October 2013. Retrieved 22 October 2013.
  28. ^ Paul G. Barash; et al., eds. (2009). Clinical anesthesia (6 ed.). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins. p. 346. ISBN 978-0-7817-8763-5.
  29. ^ a b White PF, Tang J, Song D, Coleman JE, Wender RH, Ogunnaike B, et al. (January 2007). "Transdermal scopolamine: an alternative to ondansetron and droperidol for the prevention of postoperative and postdischarge emetic symptoms". Anesthesia and Analgesia. 104 (1): 92–96. doi:10.1213/01.ane.0000250364.91567.72. PMID 17179250. S2CID 44784425.
  30. ^ Renner UD, Oertel R, Kirch W (October 2005). "Pharmacokinetics and pharmacodynamics in clinical use of scopolamine". Therapeutic Drug Monitoring. 27 (5): 655–665. doi:10.1097/01.ftd.0000168293.48226.57. PMID 16175141. S2CID 32720769.
  31. ^ "Google Scholar". scholar.google.com. Retrieved 16 December 2017.
  32. ^ "PDSP Ki Database".
  33. ^ Muranaka T, Ohkawa H, Yamada Y (1993). "Continuous Production of Scopolamine by a Culture of Duboisia leichhardtii Hairy Root Clone in a Bioreactor System". Applied Microbiology and Biotechnology. 40 (2–3): 219–223. doi:10.1007/BF00170370. S2CID 45125074.
  34. ^ a b c Ziegler J, Facchini PJ (2008). "Alkaloid biosynthesis: metabolism and trafficking". Annual Review of Plant Biology. 59 (1): 735–769. doi:10.1146/annurev.arplant.59.032607.092730. PMID 18251710.
  35. ^ Li R, Reed DW, Liu E, Nowak J, Pelcher LE, Page JE, Covello PS (May 2006). "Functional genomic analysis of alkaloid biosynthesis in Hyoscyamus niger reveals a cytochrome P450 involved in littorine rearrangement". Chemistry & Biology. 13 (5): 513–520. doi:10.1016/j.chembiol.2006.03.005. PMID 16720272.
  36. ^ Ladenburg A (1880). "Die natürlich vorkommenden mydriatisch wirkenden Alkaloïde" [The naturally occurring alkaloids that act mydriatically [i.e., to dilate the pupils]]. Annalen der Chemie (in German). 206 (3): 274–307. doi:10.1002/jlac.18812060303.; see pp. 299–307.
  37. ^ a b "TWILIGHT SLEEP; Is Subject of a New Investigation". The New York Times. 31 January 1915.
  38. ^ Finkbeiner A (31 October 1999). "Labor Dispute. Book review: What a Blessing She Had Chloroform: The Medical and Social Response to the Pain of Childbirth from 1800 to the Present". The New York Times.
  39. ^ a b c Uribe M, Moreno CL, Zamora A, Acosta P (September 2005). "Perfil epidemiológico de la intoxicación con burundanga en la clínica Uribe Cualla S. A. de Bogotá, D. C" (PDF). Acta Neurológica Colombiana (in Spanish). 21 (3): 197–201. Archived (PDF) from the original on 7 October 2016.
  40. ^ Bell V (3 March 2011). "Mind controller: What is the 'burundanga' drug?". Wired UK (published April 2011). Archived from the original on 11 August 2017.
  41. ^ "Visitors to Art of Healing exhibition told how Australian Indigenous bush medicine was given to every allied soldier landing at Normandy on D-Day". King's College London. 7 June 2019. Retrieved 2 June 2020.
  42. ^ Freye E (2010). "Toxicity of Datura Stramonium". Pharmacology and Abuse of Cocaine, Amphetamines, Ecstasy and Related Designer Drugs. Netherlands: Springer. pp. 217–218. doi:10.1007/978-90-481-2448-0_34. ISBN 978-90-481-2447-3.
  43. ^ "Bilsykemedisin i falske rohypnol-tabletter". Aftenposten.no. Archived from the original on 27 June 2008.
  44. ^ "Perth backpacker overdose linked to common anti-nausea drug". ABC News. 4 January 2018. Retrieved 4 January 2018.
  45. ^ Fatur K, Kreft S (April 2020). "Common anticholinergic solanaceaous plants of temperate Europe - A review of intoxications from the literature (1966-2018)". Toxicon. 177: 52–88. doi:10.1016/j.toxicon.2020.02.005. PMID 32217234. S2CID 213559151.
  46. ^ Preissel U, Preissel HG (2002). Brugmansia and Datura: Angel's Trumpets and Thorn Apples. Buffalo, NY: Firefly Books. pp. 106–129. ISBN 1-55209-598-3.
  47. ^ Raetsch C (2005). The encyclopedia of psychoactive plants: ethnopharmacology and its applications. US: Park Street Press. pp. 277–282.
  48. ^ Harner M (1980). The Way of the Shaman. New York: Harper & Row. ISBN 9780062503732.
  49. ^ Kuklin A (February 1999). How Do Witches Fly?. DNA Press. ISBN 0-9664027-0-7.
  50. ^ a b Hansen, Harold A. The Witch's Garden pub. Unity Press 1978 ISBN 978-0913300473
  51. ^ Sollmann T (1957). A Manual of Pharmacology and Its Applications to Therapeutics and Toxicology (8th ed.). Philadelphia and London: W.B. Saunders.
  52. ^ "Genesis 30:14–16 (King James Version)". Bible Gateway. Retrieved 6 January 2014.
  53. ^ "Song of Songs 7:12–13 (King James Version)". Bible Gateway. Retrieved 6 January 2014.
  54. ^ House RE (September 1922). "The Use of Scopolamine in Criminology". Texas State Journal of Medicine. 18: 256–263.
    Reprinted in: House RE (July–August 1931). "The Use of Scopolamine in Criminology". American Journal of Police Science. 2 (4): 328–336. doi:10.2307/1147361. JSTOR 1147361.
  55. ^ Bimmerle G (22 September 1993). "'Truth' Drugs in Interrogation". CIA.gov. Central Intelligence Agency. Archived from the original on 27 September 2012. Retrieved 14 June 2012.
  56. ^ Gazdík J, Navara L (8 August 2009). "Svědek: Grebeníček vězně nejen mlátil, ale dával jim i drogy" [A witness: Grebeníček not only beat prisoners, he also administered drugs to them] (in Czech). iDnes. Archived from the original on 11 August 2009. Retrieved 10 August 2009.
  57. ^ "Colombia 2012 Crime and Safety Report: Cartagena". Overseas Security Advisory Council, United States Department of State. 4 March 2012. Archived from the original on 15 March 2013. Retrieved 6 August 2015.
  58. ^ a b c d Domínguez I (25 July 2016). "Burundanga: the stealth drug that cancels the victim's willpower". Crime. El País, Madrid. Archived from the original on 20 August 2016. Retrieved 12 August 2016.
  59. ^ "Burundanga Business Card Drug Warning". Hoax-Slayer.com. 12 October 2008. Archived from the original on 7 March 2009.
  60. ^ "Beware the Burundanga Man!". About.com Entertainment. Archived from the original on 10 January 2017. Retrieved 19 December 2016.
  61. ^ Mikkelson D. "Burundanga/Scopolamine Warning". snopes.com. Retrieved 19 December 2016.
  62. ^ Reichert S, Lin C, Ong W, Him CC, Hameed S (May 2017). "Million dollar ride: Crime committed during involuntary scopolamine intoxication" (PDF). Canadian Family Physician. 63 (5): 369–370. PMID 28500194. Archived (PDF) from the original on 22 April 2021.
  63. ^ "World's Scariest Drug (Documentary Exclusive)". YouTube.
  64. ^ "أخطر مخدر في العالم (عدنا إلى كولومبيا)". YouTube (in Arabic).
  65. ^ "المخدر الأخطر في العالم ستتعرض له بدون أن تشعر في أمريكا اللاتينية". YouTube (in Arabic).
  66. ^ Anderson L. "Devil's Breath: Urban Legend or the World's Most Scary Drug?". Drugs.com. Retrieved 9 July 2019.
  67. ^ Saner E (2 September 2015). "'Devil's breath' aka scopolamine: can it really zombify you?". The Guardian. Retrieved 4 January 2019.
  68. ^ "Colombia Travel Advisory". travel.state.gov. Archived from the original on 5 April 2022.
  69. ^ Global Affairs Canada (16 November 2012). "Travel Advice and Advisories for Colombia". Travel.gc.ca. Archived from the original on 16 May 2022.
  70. ^ "Devil's Breath: Why Scopolamine Abuse is So Terrifying". Northpoint Washington. 9 May 2019.
  71. ^ Forest E (27 July 2008). "Atypical Drugs of Abuse". Articles & Interviews. Student Doctor Network. Archived from the original on 27 May 2013.
  72. ^ Curran HV, Pooviboonsuk P, Dalton JA, Lader MH (January 1998). "Differentiating the effects of centrally acting drugs on arousal and memory: an event-related potential study of scopolamine, lorazepam and diphenhydramine". Psychopharmacology. 135 (1): 27–36. doi:10.1007/s002130050482. PMID 9489931. S2CID 9872819.
  73. ^ Drachman DA, Leavitt J (February 1974). "Human memory and the cholinergic system. A relationship to aging?". Archives of Neurology. 30 (2): 113–121. doi:10.1001/archneur.1974.00490320001001. PMID 4359364.
  74. ^ a b Hasselmo ME, Wyble BP (December 1997). "Free recall and recognition in a network model of the hippocampus: simulating effects of scopolamine on human memory function". Behavioural Brain Research. 89 (1–2): 1–34. doi:10.1016/s0166-4328(97)00048-x. PMID 9475612. S2CID 584350.
  75. ^ a b c d e f More SV, Kumar H, Cho DY, Yun YS, Choi DK (September 2016). "Toxin-Induced Experimental Models of Learning and Memory Impairment". International Journal of Molecular Sciences. 17 (9): 1447. doi:10.3390/ijms17091447. PMC 5037726. PMID 27598124.
  76. ^ Ridley RM, Bowes PM, Baker HF, Crow TJ (1984). "An involvement of acetylcholine in object discrimination learning and memory in the marmoset". Neuropsychologia. 22 (3): 253–263. doi:10.1016/0028-3932(84)90073-3. PMID 6431311. S2CID 7110504.
  77. ^ Flicker C, Serby M, Ferris SH (February 1990). "Scopolamine effects on memory, language, visuospatial praxis and psychomotor speed". Psychopharmacology. 100 (2): 243–250. doi:10.1007/bf02244414. PMID 2305013. S2CID 24645744.
  78. ^ Lisboa SF, Vila-Verde C, Rosa J, Uliana DL, Stern CA, Bertoglio LJ, et al. (January 2019). "Tempering aversive/traumatic memories with cannabinoids: a review of evidence from animal and human studies". Psychopharmacology. 236 (1): 201–226. doi:10.1007/s00213-018-5127-x. PMID 30604182. S2CID 58655082.
  79. ^ Qin M, Zeidler Z, Moulton K, Krych L, Xia Z, Smith CB (September 2015). "Endocannabinoid-mediated improvement on a test of aversive memory in a mouse model of fragile X syndrome". Behavioural Brain Research. 291: 164–171. doi:10.1016/j.bbr.2015.05.003. PMC 5003021. PMID 25979787.
  80. ^ Lott IT (2012). "Neurological phenotypes for Down syndrome across the life span". Down Syndrome: From Understanding the Neurobiology to Therapy. Progress in Brain Research. Vol. 197. pp. 101–21. doi:10.1016/b978-0-444-54299-1.00006-6. ISBN 9780444542991. PMC 3417824. PMID 22541290.
  81. ^ Lagalwar S, Bordayo EZ, Hoffmann KL, Fawcett JR, Frey WH (1999). "Anandamides inhibit binding to the muscarinic acetylcholine receptor". Journal of Molecular Neuroscience. 13 (1–2): 55–61. doi:10.1385/jmn:13:1-2:55. PMID 10691292. S2CID 22731716.
  82. ^ Drevets WC, Zarate CA, Furey ML (June 2013). "Antidepressant effects of the muscarinic cholinergic receptor antagonist scopolamine: a review". Biological Psychiatry. 73 (12): 1156–1163. doi:10.1016/j.biopsych.2012.09.031. PMC 4131859. PMID 23200525.
  83. ^ Hasselmann H (2014). "Scopolamine and depression: a role for muscarinic antagonism?". CNS & Neurological Disorders Drug Targets. 13 (4): 673–683. doi:10.2174/1871527313666140618105710. PMID 24938776.
  84. ^ Jaffe RJ, Novakovic V, Peselow ED (2013). "Scopolamine as an antidepressant: a systematic review". Clinical Neuropharmacology. 36 (1): 24–26. doi:10.1097/wnf.0b013e318278b703. PMID 23334071. S2CID 19740245.
  85. ^ Wohleb ES, Wu M, Gerhard DM, Taylor SR, Picciotto MR, Alreja M, Duman RS (July 2016). "GABA interneurons mediate the rapid antidepressant-like effects of scopolamine". The Journal of Clinical Investigation. 126 (7): 2482–2494. doi:10.1172/JCI85033. PMC 4922686. PMID 27270172.
  86. ^ "NASA Signs Agreement to Develop Nasal Spray for Motion Sickness". NASA (Press release). 12 October 2012. Retrieved 3 February 2022.
  • Media related to Scopolamine at Wikimedia Commons
  • "Scopolamine". Drug Information Portal. U.S. National Library of Medicine.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Scopolamine&oldid=1119487008"