Scopolamine
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Scopolamine
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| Systematic (IUPAC) name | |
| (-)-(S)-3-Hydroxy-2-phenyl-propionic acid (1R,2R,4S,7S,9S)-9-methyl-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7-yl ester | |
| Identifiers | |
| CAS number | 51-34-3 |
| ATC code | A04AD01 N05CM05, S01FA02 |
| PubChem | 5184 |
| DrugBank | APRD00616 |
| Chemical data | |
| Formula | C17H21NO4 |
| Mol. mass | 303.353 g/mol |
| Pharmacokinetic data | |
| Bioavailability | 10 - 50% [1] |
| Metabolism | ? |
| Half life | 4.5 hours[1] |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
C(US) |
| Legal status | |
| Routes | transdermal, ocular, oral, subcutaneous, intravenous |
Scopolamine, also known as hyoscine is a tropane alkaloid drug with muscarinic antagonist effects. It is obtained from plants of the family Solanaceae (nightshades), such as henbane, jimson weed and Angel's Trumpets (Datura resp. Brugmansia spec.), and corkwood (Duboisia species [2]). It is among the secondary metabolites of these plants. Therefore, scopolamine is one of three active components of belladonna and stramonium tinctures and powders used medicinally along with atropine and hyoscyamine.
Scopolamine is 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 micrograms (µg) per day.
Scopolamine has about 92 per cent of the antimuscarinic power of atropine at equivalent doses and may impact nicotinic acetylcholine receptors in a clinically significant degree as well. It crosses the blood-brain barrier and can produce CNS effects which are similar to those of ethanolamine class antihistamines such as diphenhydramine, which was in fact discovered in a search for a synthetic analogue of scopolamine.
An overdose can cause delirium, delusions, paralysis, dangerous elevations of body temperature, stupor and death.
Contents |
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;[citation needed] 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 these uses:
- Primary:
- Treatment of nausea and motion sickness
- Treatment of intestinal cramping
- For ophthalmic purposes.
- As a general depressant and adjunct to narcotic painkillers
- Less often:
- As a preanesthetic agent
- Uncommonly, for some forms of Parkinsonism.
- 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[citation needed].
- To enhance the pain-killing ability of various opioids.
- 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.[citation needed]
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 spatial 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[citation needed] due to its amnesic effect. Scopolamine causes memory impairments to a similar degree as diazepam.[2]
- 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 within a few days, and the improvement lasted for at least a week after switching to a placebo.[3]
- Due to its effectiveness against sea-sickness it has become commonly used by scuba divers.[4][5]
Routes of administration
Scopolamine can be administered by transdermal patches,[6] 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[citation needed] as well as to potentiate this and other effects of morphine, methadone, hydromorphone, oxycodone and other opioids.[citation needed] It is therefore occasionally seen as a recreational drug. The use of medical scopolamine/opioid combination preparations for euphoria is uncommon but does exist and can be seen in conjunction with opioid use.[citation needed]
Another separate group of users prefer dangerously high doses, especially in the form of datura preparations, for the deliriant and hallucinogenic effects. The hallucinations produced by scopolamine, in common with other potent anticholinergics, are especially real-seeming, repetitive, boring and unpleasant. An overdose of scopolamine is also physically exceedingly unpleasant and can be fatal, unlike the effect of other more commonly used hallucinogens. For these reasons, naturally occurring anticholinergics are rarely used for recreational purposes.[citation needed]
Scopolamine in transdermal, oral, sublingual, and injectable formulations can produce a cholinergic rebound effect when high doses are stopped. This is the opposite of scopolamine's therapeutic effects: sweating, runny nose, abdominal cramps, nausea, vomiting, vertigo, dizziness, irritability, and diarrhea. Psychological dependence is also possible when the drug is taken for its tranquilizing effects.[citation needed]
Potential use in interrogation
"The Use of Scopolamine in Criminology" by Robert E. House appeared in the Texas State Journal of Medicine in September, 1922 and was reprinted in The American Journal of Police Science, Vol. 2, No. 4, Jul. - Aug., 1931.[citation needed]
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.[citation needed]
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.[citation needed]
Scopolamine has been used under the name burundanga in Venezuelan and Thailand resorts in order to drug and then rob tourists. While there are unfounded rumors that delivery mechanisms include using pamphlets and flyers laced with the drug, not enough is readily absorbed through the skin to have an effect. However, spiked alcoholic drinks are occasionally used. In recent years the criminal use of scopolamine has become an epidemic. Approximately half of emergency room admissions for poisoning in Bogotá have been attributed to scopolamine.[7][citation needed]
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.[citation needed]
In June 2008, more than 20 people were hospitalized with psychosis in Norway after ingesting counterfeit Rohypnol tablets containing Scopolamine. 11
Shamanic use
In Colombia a plant admixture containing scopolamine called Burundanga has been used shamanically for decades.[citation needed]
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 patient only able to make raccoon-like noises, thirst, blurred vision and sensitivity to light, constipation, difficulty urinating and tachycardia. Other effects of overdose include flushing and fever, as well as excitement, restlessness, hallucinations, or delirium. 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.[citation needed]
Use in scuba diving to prevent sea sickness has led to the discovery of another side effect[citation needed]. In deep water, below 50–60 feet, some divers have reported pain in the eyes that subsides quickly if the diver ascends to a depth of 40 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 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.[citation needed]
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 from the 1940s to the 1960s to put mothers in labor into a kind of "twilight sleep" that did not stop pain, but merely eliminated the memory of pain by attacking the brain functions responsible for self-awareness and self-control. Often, this caused a kind of psychosis, followed by post-traumatic stress-like memories in thousands of new mothers.[8][citation needed]
Scopolamine was an ingredient used in some over-the-counter sleep aids before 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, etc.
Popular culture
- (1940) In one of crime fiction's all-time classic novels, Farewell, My Lovely (1940) by Raymond Chandler, 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 identity of Velma and the whereabouts of Moose Malloy).
- "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)
- "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")
- 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 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.
- 1972: In Fear and Loathing In Las Vegas by Hunter S. Thompson, the narrator's attorney mentions an incident in which he was given an entire datura root as a gift, at the entire thing at once and went blind, had to be taken back to to house in a wheelbarrow and started making noises like a raccoon.
- 1974: In episode 1 "That'll Be The Day", of the fourth series of the 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.
- 1990s: The X-Files Red Museum shows Scopolamine as a suspect agent in usage for kidnappings.
- 1990: Scopolamine is mentioned by the villain Cain as one of the cutting agents of the drug Nuke in Robocop 2
- 1994: In the book Blood Hunt by Ian Rankin (written under the pseudonym Jack Harvey) scopolamine, under the name Burundanga is used by the main Character, Gordon Reeve, to gain information and access to facilities in order to find his brother's killer.[9]
- 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 "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", one character in the TV show House, M.D. is shown wearing a scopolamine patch.
- 2008: In the TV series Knight Rider 2008, in episode 4, "A Hard Day's Knight", Mike Knight is poisoned with hyoscine, and needs to find an antidote within 3 hours.
- 2008: In the TV series My Own Worst Enemy, in episode 2, "The Hummingbird", Henry is poisoned with scopalamine and is told he must have his heart shocked within the next minute or he will die.
External links
- The Erowid Scopolamine Vault
- Scopolamine Transdermal Patch Information:
- Sober Circle Article on Dangers of Scopolamine
References
- ^ a b Putcha L, Cintrón NM, Tsui J, Vanderploeg JM, Kramer WG (June 1989). "Pharmacokinetics and oral bioavailability of scopolamine in normal subjects". Pharm. Res. 6 (6): 481–5. doi:10.1023/A:1015916423156. PMID 2762223.
- ^ Jones DM; Jones ME, Lewis MJ, Spriggs TL. (May 1979). "Drugs and human memory: effects of low doses of nitrazepam and hyoscine on retention.". Br J Clin Pharmacol. 7 (5): 479–83. PMID 475944.
- ^ Furey, ML; Drevets, WC (October 2006). "Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial". Archives of General Psychiatry, vol 63, p 1121 63: 1121. doi:10.1001/archpsyc.63.10.1121. PMID 17015814, 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.
- ^ Bitterman N, Eilender E, Melamed Y (May 1991). "Hyperbaric oxygen and scopolamine". Undersea Biomed Res 18 (3): 167–74. PMID 1853467, http://archive.rubicon-foundation.org/2573. Retrieved on 13 August 2008.
- ^ Williams TH, Wilkinson AR, Davis FM, Frampton CM (March 1988). "Effects of transcutaneous scopolamine and depth on diver performance". Undersea Biomed Res 15 (2): 89–98. PMID 3363755, http://archive.rubicon-foundation.org/2495. Retrieved on 13 August 2008.
- ^ White PF, Tang J, Song D, et al (2007). "Transdermal scopolamine: an alternative to ondansetron and droperidol for the prevention of postoperative and postdischarge emetic symptoms". Anesth. Analg. 104 (1): 92–6. doi:10.1213/01.ane.0000250364.91567.72. PMID 17179250, http://www.anesthesia-analgesia.org/cgi/pmidlookup?view=long&pmid=17179250.
- ^ Wall Street Journal, July 3, 1995
- ^ The Business of Being Born, [1]
- ^ Rankin, Ian. Blood Hunt. Little, Brown and Company, New York: 1994.
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