Scopolamine

Effects

Overview

The main active compound in datura, medium and high doses have serious side effects and cause extremely unpleasant deleriant hallucinations. Avoid it. TS

Scopolamine, also known as hyoscine, or Devil's Breath, is a muscarinic antagonist and tropane alkaloid 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 orally and as a transdermal patch since it has been long known to have transdermal bioavailability.[1–6] WP

Scopolamine is in the muscarinic acetylcholine antagonist group of drugs and works by blocking the binding of acetylcholine within the central nervous system and peripheral tissues.[5] WP

Scopolamine was first written about in 1881 and started to be used for anesthesia around 1900. 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 in higher doses. In these contexts, its mind-altering effects have been utilized for recreational and occult purposes. 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, or black henbane. It is on the World Health Organization's List of Essential Medicines.[4][7–14] WP

History

History

Plants naturally containing scopolamine such as Atropa belladonna (deadly nightshade), Brugmansia (angels trumpet), Datura (Jimson weed), Hyoscyamus niger, Mandragora officinarum, Scopolia carniolica, Latua and Duboisia myoporoides have been known about and used for various purposes in both the New and Old Worlds since ancient times. 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, and as various preparations from its plant-based form since antiquity and perhaps prehistoric times.[11][15][16][17] WP

In 1899, Schneiderlin recommended the use of scopolamine and morphine for surgical anaesthesia, and it started to be used sporadically for that purpose. 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. 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". 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". It remained widely used in the US until the 1960s, when growing chemophobia and a desire for more natural childbirth led to its abandonment.[7][18][19][20] WP

Legal status

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.[10][21] WP

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.[22] WP

Interrogation

Investigations on potential use of scopolamine as a truth serum during interrogations were conducted in the early 20th century, and were ultimately dropped because of the side effects. 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.[23–26] WP

Pharmacology

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.[27][28] WP

In doses higher than intended for medicinal use, the hallucinogenic alteration of consciousness, as well as the delirium 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 associated solely with the antagonism of postsynaptic M₁ receptors; currently no other receptor subtypes have been implicated.[29] WP

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. 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.[29][30] WP

Although often broadly referred to as simply being 'anticholinergic', antimuscarinic would be more specific and accurate terminology to use for scopolamine, as, for example, it is not known to block nicotinic receptors.[29] WP

Pharmacokinetics

Scopolamine undergoes first-pass metabolism and about 2.6% is excreted unchanged in urine. It has a bioavailability of 20–40%, reaches peak plasma concentration in about 45 minutes, and in healthy subjects has an average half-life of 5 hours (observed range 2–10 hours). Scopolamine is primarily metabolized by the CYP3A4 enzyme, and grapefruit juice decreases metabolism of scopolamine, consequently increasing plasma concentration.[31][32] WP

Chemistry

Formula

C17H21NO4 PC

CAS number

51-34-3 PC

Molar mass (g/mol)

303.35 PC

IUPAC name (computed by PubChem)

[(1S,2S,4R,5R)-9-methyl-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-7-yl] (2S)-3-hydroxy-2-phenylpropanoate PC

SMILES

CN1[C@@H]2CC(C[C@H]1[C@H]3[C@@H]2O3)OC(=O)[C@H](CO)C4=CC=CC=C4 PC

InChIKey

STECJAGHUSJQJN-USLFZFAMSA-N PC

PubChem CID

3000322

Pop culture

No references added yet.

References

1. Other Juo PS. Concise Dictionary of Biomedicine and Molecular Biology. 2001
2. Other Duffy R. Colombian Devil's Breath. 23 July 2007
3. Other About hyoscine hydrobromide. 24 October 2022
4. Other Osbourn AE, Lanzotti V. Plant-derived Natural Products: Synthesis, Function, and Application. 2009
5. Other Scopolamine
6. Other Sollmann T. A Manual of Pharmacology and Its Applications to Therapeutics and Toxicology. 1957
7. Other Keys TE. The history of surgical anesthesia. 1996
8. Other Fischer J, Ganellin CR. Analogue-based Drug Discovery. 2006
9. Other Kennedy DO. Plants and the Human Brain. 2014
10. Journal / agency Uribe-Granja MG, Moreno-López CL, Zamora-Suárez A, Acosta PJ. Perfil epidemiológico de la intoxicación con burundanga en la clínica Uribe Cualla S. A. de Bogotá, D. C. Acta Neurológica Colombiana. September 2005
11. Other Rätsch, Christian. The Encyclopedia of Psychoactive Plants: Ethnopharmacology and Its Applications. 2005
12. Other The Chambers Dictionary. 1998
13. Other Cattell HW. Lippincott's new medical dictionary. 1910
14. Other Organization WH. The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). 2023
15. Other Armando T. Hunziker: The Genera of Solanaceae. A.R.G. Gantner Verlag K.G., Ruggell, Liechtenstein 2001 ISBN 3-904144-77-4
16. Other Pharmacognosy and Phytochemistry: Drugs Containing Alkaloids
17. Journal / agency Ladenburg A. Die natürlich vorkommenden mydriatisch wirkenden Alkaloïde. Justus Liebigs Annalen der Chemie. January 1881. doi:10.1002/jlac.18812060303
18. Journal / agency Twilight Sleep: the Dammerschlaf of the Germans. Canadian Medical Association Journal. September 1915. PMID 20310688 · PMC1584452
19. Other TWILIGHT SLEEP; Is Subject of a New Investigation. 31 January 1915
20. Other Finkbeiner A. 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. 31 October 1999
21. Other Bell V. Mind controller: What is the 'burundanga' drug?. 3 March 2011
22. Other Visitors to Art of Healing exhibition told how Australian Indigenous bush medicine was given to every allied soldier landing at Normandy on D-Day. 7 June 2019
23. Journal / agency House RE. The Use of Scopolamine in Criminology. Texas State Journal of Medicine. September 1922
24. Journal / agency House RE. The Use of Scopolamine in Criminology. American Journal of Police Science. July–August 1931. doi:10.2307/1147361
25. Other Bimmerle G. 'Truth' Drugs in Interrogation. 22 September 1993
26. Other Gazdík J, Navara L. Svědek: Grebeníček vězně nejen mlátil, ale dával jim i drogy. 8 August 2009
27. Other Google Scholar
28. Other PDSP Ki Database
29. Journal / agency Dawson AH, Buckley NA. Pharmacological management of anticholinergic delirium - theory, evidence and practice. British Journal of Clinical Pharmacology. March 2016. doi:10.1111/bcp.12839 · PMID 26589572 · PMC4767198
30. Journal / agency Lessenger JE, Feinberg SD. Abuse of prescription and over-the-counter medications. Journal of the American Board of Family Medicine. 2008. doi:10.3122/jabfm.2008.01.070071 · PMID 18178702
31. Journal / agency Putcha L, Cintrón NM, Tsui J, Vanderploeg JM, Kramer WG. Pharmacokinetics and oral bioavailability of scopolamine in normal subjects. Pharmaceutical Research. June 1989. doi:10.1023/A:1015916423156 · PMID 2762223
32. Journal / agency Renner UD, Oertel R, Kirch W. Pharmacokinetics and pharmacodynamics in clinical use of scopolamine. Therapeutic Drug Monitoring. October 2005. doi:10.1097/01.ftd.0000168293.48226.57 · PMID 16175141

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