Scopolamine 28979 226130576 2008-07-16T23:17:22Z 99.163.93.193 /* Recreational use */ {{Refimprove|date=July 2008}} :''The fictional truth drug [[Hyoscine-pentothal]] does not describe real hyoscine accurately.'' {{drugbox | IUPAC_name = (-)-(''S'')-3-Hydroxy-2-phenyl-propionic acid (1''R'',2''R'',4''S'',7''S'',9''S'')-9-methyl-3-oxa-9-aza-tricyclo[3.3.1.0<sup>2,4</sup>]non-7-yl ester | image = L-Scopolamin.svg | width = 178 | CAS_number = 51-34-3 | ATC_prefix = A04 | ATC_suffix = AD01 | ATC_supplemental = {{ATC|N05|CM05}}, {{ATC|S01|FA02}} | PubChem = 5184 | DrugBank = APRD00616 | C=17 | H=21 | N=1 | O=4 | molecular_weight = 303.353 g/mol | bioavailability = 10 - 50% <ref name="pmid2762223">{{cite journal |author=Putcha L, Cintrón NM, Tsui J, Vanderploeg JM, Kramer WG |title=Pharmacokinetics and oral bioavailability of scopolamine in normal subjects |journal=Pharm. Res. |volume=6 |issue=6 |pages=481–5 |year=1989 |month=June |pmid=2762223 | doi = 10.1023/A:1015916423156 <!--Retrieved from CrossRef by DOI bot-->|url= }}</ref> | protein_bound = | metabolism = | elimination_half-life = 4.5 hours<ref name="pmid2762223">{{cite journal |author=Putcha L, Cintrón NM, Tsui J, Vanderploeg JM, Kramer WG |title=Pharmacokinetics and oral bioavailability of scopolamine in normal subjects |journal=Pharm. Res. |volume=6 |issue=6 |pages=481–5 |year=1989 |month=June |pmid=2762223 | doi = 10.1023/A:1015916423156 <!--Retrieved from CrossRef by DOI bot-->|url= }}</ref> | pregnancy_US = C | legal_US = Rx-only | legal_UK = P | routes_of_administration = transdermal, ocular, oral, subcutaneous, intravenous }} '''Scopolamine''', also known as '''hyoscine''' and "Devils Breath", is a [[tropane alkaloid]] [[Medication|drug]] with [[muscarinic antagonist]] effects. It is obtained from plants of the family [[Solanaceae]] (nightshades), such as [[henbane]] or jimson weed (''[[Datura]]'' species). It is among the [[secondary metabolites]] of these plants. The drug can be highly toxic due its powerful [[anticholinergic]] properties and has legitimate medical applications in very minute doses. As an example, in the treatment of [[motion sickness]], the dose, gradually released from a [[transdermal patch]], is only 330 [[microgram]]s (µg) per day. An overdose can cause [[delirium]], [[delusion]]s, [[paralysis]], [[stupor]] and death. ==Etymology== Scopolamine is named after the plant [[genus]] ''[[Scopolia]]''. The name "hyoscine" is from the scientific name for [[henbane]], ''Hyoscyamus niger''. ==Physiology== Scopolamine acts as a competitive antagonist at specific [[muscarinic acetylcholine receptors]], specifically [[M1 receptors]]; it is thus classified as an [[anticholinergic]], or, more specifically, as an [[anti-muscarinic]] drug. (See the article on the [[parasympathetic]] nervous system for details of this physiology.) ==Medical use== In [[medicine]], scopolamine has three primary uses: treatment of [[nausea]] and [[motion sickness]], treatment of [[intestinal cramping]], and for ophthalmic purposes. Use as a general depressant and adjunct to narcotic painkillers is also common. The drug is less commonly used as a [[preanesthetic agent]] and uncommonly for some forms of [[Parkinsonism]]. Scopolamine is also used as an adjunct to narcotic analgesia, such as the product [[Twilight Sleep]] which contained [[morphine]] and scopolamine, some of the original formulations of [[Percodan]] and some European brands of [[methadone]] injection, as well as use of tablets or patches to combat nausea as well as enhance the pain-killing ability of various [[opioids]]. Scopolamine can be used as an occasional sleep aid and was available in some over the counter products in the United States for this purpose until November 1990. ===Nausea=== Its use as an antiemetic in the form of a [[transdermal patch]] is the drug's most common medical application in the United States. {{Fact|date=July 2008}} ===Ophthalmic=== The drug is used in eye drops to induce [[mydriasis]] (pupillary dilation) and [[cycloplegia]] (paralysis of the eye focusing muscle), primarily in the treatment of eye disorders that benefit from its prolonged effect, e.g. [[uveitis]], [[iritis]], [[iridocyclitis]], etc. ===Memory research=== Because of its anticholinergic effects, scopolamine has been shown to prevent the activation of [[medial temporal lobe]] structures for novel stimuli during [[working memory]] tasks. ===Nicotine addiction=== Scopolamine is being investigated for its possible usefulness alone or in conjunction with other drugs in assisting people in breaking the [[nicotine]] habit. The mechanism by which it mitigates withdrawal symptoms appears to be at least partially different from that of [[clonidine]] meaning that the two drugs can be used together without duplicating or cancelling out the effects of each other. ===Other medical uses=== *It can be used as a depressant of the [[central nervous system]], and was formerly used as a bedtime sleep aid. *[[Anesthetic]]; Its use in general anesthesia is favored by some{{Fact|date=November 2007}} due to its [[amnesic]] effect. Scopolamine causes memory impairments to a similar degree as [[diazepam]].<ref>{{cite journal |author=Jones DM |coauthors=Jones ME, Lewis MJ, Spriggs TL. |title=Drugs and human memory: effects of low doses of nitrazepam and hyoscine on retention. |journal=Br J Clin Pharmacol. |volume=7 |issue=5 |pages=479–83 |month=May |year=1979 |pmid=475944}}</ref> *In [[otolaryngology]] it is used to dry the upper airway (anti-sialogogue action) prior to instrumentation of the airway. *In October 2006 researchers at the US [[National Institute of Mental Health]] found that scopolamine reduced symptoms of [[depression (mood)|depression]] within a few days, and the improvement lasted for at least a week after switching to a [[placebo]].<ref>{{cite journal | last = Furey | first = ML | coauthors = Drevets, WC | title = Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial | journal = Archives of General Psychiatry, vol 63, p 1121 | volume = 63 | pages = 1121 | date= October 2006 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?orig_db=PubMed&db=PubMed&cmd=Search&term=%22Archives+of+general+psychiatry%22%5BJour%5D+AND+63%5Bvolume%5D+AND+1121%5Bpage%5D | doi = 10.1001/archpsyc.63.10.1121 | pmid = 17015814 }}</ref> *Due to its effectiveness against [[sea-sickness]] it has become commonly used by [[Scuba set|scuba]] divers. ===Routes of administration=== Scopolamine can be administered by [[transdermal patch]]es,<ref name="pmid17179250">{{cite journal |author=White PF, Tang J, Song D, ''et al'' |title=Transdermal scopolamine: an alternative to ondansetron and droperidol for the prevention of postoperative and postdischarge emetic symptoms |journal=Anesth. Analg. |volume=104 |issue=1 |pages=92–6 |year=2007 |pmid=17179250 |doi=10.1213/01.ane.0000250364.91567.72 |url=http://www.anesthesia-analgesia.org/cgi/pmidlookup?view=long&pmid=17179250}}</ref> oral, subcutaneous, [[ophthalmic]] and [[intravenous]] routes. The transdermal patch for prevention of nausea and motion sickness employs scopolamine base. The oral, ophthalmic and intravenous forms are usually scopolamine [[hydrobromide]] (for example in [[Donnatal]]). ==Recreational use== Scopolamine, in common with the large percentage of anticholinergics which cross the blood-brain barrier such as [[diphenhydramine]], [[dicyclomine]], [[trihexyphenidyl]] and related drugs, is said to produce euphoria at and around therapeutic doses as well as to potentiate this and other effects of [[morphine]], [[methadone]], [[hydromorphone]], [[oxycodone]] and other opioids. It is therefore occasionally seen as a recreational drug. The use of medical scopolamine (most often in the form of tablets) for euphoria is uncommon but does exist and can be seen in conjunction with opioid use. Another separate group of users prefer dangerously high doses, especially in the form of [[datura]] or [[belladonna]] preparations, for the deliriant and hallucinogenic effects. The hallucinations produced by scopolamine, in common with other potent anticholinergics, are especially real-seeming and create a perception of a new world filled with frenzied energy. The difference in realism of hallucinations caused by [[anticholinergics]] such as scopolamine and other [[hallucinogens]] such as the [[phenethylamines]] or dissociatives like PCP is quite large. Additionally, an overdose of scopolamine can quite often be fatal, unlike other more commonly used hallucinogens. For these reasons, naturally occurring anticholinergics are rarely used for recreational purposes. ==Potential use in interrogation== The use of scopolamine as a ''[[truth drug]]'' was investigated in the 1950s by various [[intelligence agencies]], including the [[CIA]] as part of [[Project MKULTRA]]. Nazi doctor [[Josef Mengele]] experimented on scopolamine as an interrogation drug.{{Fact|date=September 2007}} ==Criminal use== Traces of scopolamine were found in the body found in the cellar of [[Hawley Harvey Crippen]], executed for the murder of his wife. It is unclear whether this caused death, and there is said to be some doubt that the body found was that of his wife. Scopolamine has been used under the name [[burundanga]] in [[Venezuela]]n and [[Thailand]] resorts in order to drug and then rob tourists. While there are unfounded rumours that delivery mechanisms include using [[pamphlet]]s and [[Flyer (pamphlet)|flyer]]s laced with the drug, not enough is readily absorbed through the skin to have an effect. However, spiked alcoholic drinks are occasionally used. <ref>[http://www.snopes.com/horrors/mayhem/burundanga.asp Snopes Burudanga rumour page]</ref><ref>[http://travel.timesonline.co.uk/tol/life_and_style/travel/your_say/article3287518.ece The 13 best travel scams - Times Online<!-- Bot generated title -->]</ref> In recent years the criminal use of scopolamine has become an epidemic. Approximately fifty percent of emergency room admissions for poisoning in [[Bogotá]] have been attributed to scopolamine.<ref>Wall Street Journal, July 3, 1995</ref> Victims of this crime are often admitted to a hospital in police custody, under the assumption that the patient is experiencing a psychotic episode. A telltale sign is a fever accompanied by a lack of sweat.{{Fact|date=July 2008}} Scopolamine is used criminally as a date rape drug and as an aid to robbery,<ref>http://www.sobercircle.com/index.asp?node=resources&section=articles&fileid=8| Retrieved 20/11/07</ref> the most common act being the clandestine drugging of a victim's drink<ref>http://www.sobercircle.com/index.asp?node=resources&section=articles&fileid=8| Retrieved 20/11/07</ref>. It is preferred because it induces [[anterograde amnesia]], or an inability to recall events a certain amount of time after its administration or during the time of intoxication. In June 2008, more than 20 people were hospitalized with psychosis in [[Norway]] after ingesting counterfeit Rohypnol tablets containing Scopolamine. [http://www.aftenposten.no/nyheter/iriks/article2507100.ece 11] ==Shamanic use== In [[Colombia]] a plant admixture containing scopolamine called ''Burundanga'' has been used [[shamanism|shamanically]] for decades. ==Adverse effects== The common side effects are related to the anticholinergic effect on [[parasympathetic]] postsynaptic receptors: dry mouth, throat and nasal passages in overdose cases progressing to impaired speech which can reach the extreme of the victim only being able to emit noises which sound like the vocalisations of a [[raccoon]], thirst, blurred vision and sensitivity to light, [[constipation]], difficulty urinating and [[tachycardia]]. Other effects include flushing and fever, as well as excitement, restlessness, hallucinations, or [[delirium]], especially with higher doses. These side effects are commonly observed with oral or parenteral uses of the drug and generally not with topical ophthalmic use. An extreme adverse reaction to ultra-high doses of drugs and other preparations containing scopolamine is temporary blindness which can last up to 72 hours. The fever and dryness associated with scopolamine has caused some recreational users to stumble into bodies of water and drown on occasion. Sometimes side effects of scopolamine can be mistaken for symptoms of [[cancer]] because of the nausea and [[anisocoria]] associated with brain tumors. However, scopolamine induced [[anisocoria]] clears up usually within 3 days. Use in scuba diving to prevent [[sea sickness]] has led to the discovery of another [[Adverse effect (medicine)|side effect]]{{Fact|date=September 2007}}. In deep water, below 50&ndash;60&nbsp;feet, some divers have reported [[pain]] in the eyes that subsides quickly if the diver ascends to a depth of 40&nbsp;feet or less. Mydriatics can precipitate an attack of [[glaucoma]] in susceptible patients, so the medication should be used with extra caution among divers who intend to go below 50&nbsp;feet. === Drug interactions === When combined with [[morphine]], it produces [[amnesia]] and a tranquilized state known as [[twilight sleep]]. Although originally used in [[obstetrics]], it is now considered dangerous for that purpose for both mother and baby. == History == Scopolamine was one of the active ingredients in [[Asthmador]], an over the counter smoking preparation marketed in the 1950s and 60's claiming to combat [[asthma]] and [[bronchitis]]. Scopolamine was used in the [[1940]]s through the [[1960]]s that put mothers in labor into a kind of "[[twilight sleep]]" that didn’t stop pain, but merely eliminated the memory of pain by attacking the brain functions responsible for self-awareness and self-control. Often, this resulted in a kind of [[psychosis]], followed by [[post-traumatic stress]]-like memories in thousands of new mothers.<ref>''The Business of Being Born,'' [http://www.babystepsonline.net/BoBB.htm]</ref> Scopolamine was an ingredient used in some over-the-counter sleep aids prior to November 1990 in the United States, when the FDA forced several hundred ingredients allegedly not known to be effective off the market. Scopolamine shared a small segment of this market with [[diphenhydramine]], [[phenyltoloxamine]], [[pyrilamine]], [[doxylamine]] and other first generation [[antihistamines]], many of which are still used for this purpose in drugs like Sominex, [[Tylenol PM]], [[NyQuil]] and so on. == Popular culture == * (1940) In one of crime fiction's all-time classic novels, ''[[Farewell, My Lovely]]'' (1940) by [[Raymond Chandler]], [[Philip Marlowe|Marlowe]] gets shot full of Scopolamine in a private sanitarium in order to both shut him up, and to pump him for knowledge, when he gets too close to the truth on a case, or rather several cases entangled into one another, that he is working on (the idenity of Velma and the whereabouts of Moose Malloy). <blockquote> "I had been shot full of dope to keep me quiet. Perhaps scopolamine too, to make me talk." (quote by Marlowe in ''Farewell, My Lovely'') </blockquote> <blockquote> "There's a drug called scopolamine, truth serum, that sometimes makes people talk without their knowing it. It's not sure fire, any more than hypnotism is. But it sometimes works." (quote by Marlowe in "Farewell, My Lovely") </blockquote> * (1957) In popular culture, scopolamine has achieved a moderate level of notoriety via its mention in the film ''[[I Was a Teenage Werewolf]]'', where Dr. Alfred Brandon uses it as part of his endeavor to regress the titular character to his "primitive roots." * (1961) Scopolamine is featured in the World War II action classic ''[[The Guns of Navarone (film)|The Guns of Navarone]]'' as a [[Schutzstaffel]] truth serum. * (1968) Scopolamine is featured in the World War II action classic ''[[Where Eagles Dare]]'' as a [[Schutzstaffel]] truth serum. * (1968) In [[Carlos Castaneda]]'s series of books ''The Teachings of Don Juan: A Yaqui Way of Knowledge'', the ''[[Datura]]'' plant is the favored shamanic, revelatory drug of the titular character. The book explores, in depth, Castaneda's experiences under the influence of the drug, as well as the rites surrounding its use and preparation. * (1974) In episode 1 "That'll Be The Day", of the fourth series of the TV Series [[Callan (TV series)|Callan]], Callan is interrogated by the KGB using the drug Scopolamine as a truth serum. * (1979) Scopolamine is also mentioned several times in [[Robert Ludlum]]'s ''[[Matarese Dynasty]]'', a fictional spy novel in which the drug is known for its uses as a truth serum. * (1990) Scopolamine is mentioned by the villain Cain as one of the cutting agents of the drug Nuke in ''[[Robocop 2]]'' * (1990s) The X-Files [[Red Museum]] shows Scopolamine as a suspect agent in usage for kidnappings. * (2000) In the pilot episode for Season 1 of [[CSI: Crime Scene Investigation]], a female thief seduces a man to sleep with her. She applies scopolamine to her [[nipples]], which knocks the man out when he ingests it orally. After she robs him and makes her escape, the scopolamine which she absorbed into her skin causes her to pass out as well. * (2000) Scopolamine was the drug Michael claimed he was injected with either by the military and/or the aliens in "[http://www.metatech.org/TheMarsRecords.pdf The Mars Records]". It might be worth noting in this context that scopolamine can cause [[confabulation]] (the mixing of memory and facts). * (2007) In the episode "[[Airborne (House episode)|Airborne]]", one character in the TV show ''[[House (TV series)|House, M.D.]]'' is shown wearing a scopolamine patch. == External links == * [http://www.erowid.org/chemicals/scopolamine/scopolamine.shtml The Erowid Scopolamine Vault] * [http://www.transdermscop.com/infomed_prescribing.htm Scopolamine Transdermal Patch Information:] * [http://www.sobercircle.com/index.asp?node=resources&section=articles&fileid=8 Sober Circle Article on Dangers of Scopolamine] == References == {{reflist}} {{ancient anaesthesia-footer}} {{Antiemetics and antinauseants}} {{Hypnotics and sedatives}} {{Mydriatics and cycloplegics}} {{Deliriants}} [[Category:Natural tropane alkaloids]] [[Category:Deliriants]] [[Category:Muscarinic antagonists]] [[Category:Epoxides]] [[Category:Plant toxins]] [[Category:Mind control]] [[cs:Skopolamin]] [[de:Scopolamin]] [[es:Escopolamina]] [[fr:Scopolamine]] [[it:Scopolamina]] [[lt:Skopolaminas]] [[hu:Szkopolamin]] [[nl:Scopolamine]] [[ja:スコポラミン]] [[pl:Skopolamina]] [[pt:Escopolamina]] [[ro:Scopolamină]] [[ru:Скополамин]] [[sk:Skopolamín]] [[sv:Skopolamin]] [[tr:Skopolamin]]