Scopolamine

Scopolamine

Systematic (IUPAC) name
(–)-(S)-3-hydroxy-2-phenylpropionic acid(1R,2R,4S,7S,9S)-9-methyl-3-oxa-9-azatricyclo[3.3.1.02,4]non-7-yl ester
Clinical data
Trade names	Transdermscop
AHFS/Drugs.com	monograph
Pregnancy cat.	C (US)
Legal status	℞-only (US)
Routes	transdermal, ocular, oral, subcutaneous, intravenous, sublingual, rectal, buccal transmucousal, intramuscular
Pharmacokinetic data
Bioavailability	10 - 50%
Half-life	4.5 hours
Identifiers
CAS number	51-34-3 Y
ATC code	A04AD01 N05CM05, S01FA02
PubChem	CID 5184
IUPHAR ligand	330
DrugBank	DB00747
ChemSpider	10194106 Y
UNII	DL48G20X8X Y
KEGG	D00138 Y
ChEBI	CHEBI:16794 Y
ChEMBL	CHEMBL1201069 N
Chemical data
Formula	C17H21NO4
Mol. mass	303.353 g/mol
SMILES	eMolecules & PubChem
InChI 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 Y Key:STECJAGHUSJQJN-FWXGHANASA-N Y
N (what is this?)  (verify)

Scopolamine, also known as levo-duboisine, and hyoscine, is a tropane alkaloid drug with muscarinic antagonist effects. It is among the secondary metabolites of plants from Solanaceae (nightshade) family of plants, such as henbane, jimson weed and Angel's Trumpets (Datura or Brugmansia), and corkwood (Duboisia). Although scopolamine is sometimes portrayed in the media as a dangerous drug, its anticholinergic properties give it some legitimate medical applications in very minute doses. An example is the treatment of motion sickness by use of a transdermal patch.

Etymology

Scopolamine is named after the plant genus Scopolia. The name "hyoscine" is from the scientific name for henbane, Hyoscyamus niger.

Biosynthesis in plants

The biosynthesis of scopolamine begins with the decarboxylation of L-ornithine to putrescine by ornithine decarboxylase (EC 4.1.1.17). Putrescine is methylated to N-methylputrescine by putrescine N-methyltransferase (EC 2.1.1.53).

A putrescine oxidase (EC 1.4.3.10) that specifically recognizes methylated purtrescine catalizes 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 enzmyatic activity could be demonstrated that catalyzes this reaction. Hygrine further rearranges to tropinone.

Subsequently, Tropinone reductase I (EC 1.1.1.206) converts tropinone to tropine which condenses with phenylalanine-derived phenyllactate to littorine. A cytochrome P450 classified as Cyp80F1 oxidizes and rearranges littorine to hyoscyamine aldehyde. In the final step, hyoscyamine undergoes epoxidation which is catalyzed by 6beta-hydroxyhyoscyamine epoxidase (EC 1.14.11.14) yielding scopolamine.

Biosynthesis of scopolamine in plants.

Methods of administration

Scopolamine can be administered orally, subcutaneously, opthalmically and intravenously, as well as via a transdermal patch. The transdermal patch (e.g., Transderm Scōp) for prevention of nausea and motion sickness employs scopolamine base, and is effective for up to 3 days.

Medical use

Addiction

Scopolamine has been used in the past to treat addiction to drugs such as heroin and cocaine. The patient was given frequent doses of scopolamine until they were delirious. This treatment was maintained for 2 to 3 days after which they were treated with pilocarpine. After recovering from this they were said to have lost the acute craving to the drug to which they were addicted.

Other medical uses

• Scopolamine causes memory impairments to a similar degree as diazepam.
• 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.
• Intravenously administered scopolamine has been found to be effective against major depressive disorder. A phase II clinical trial of its efficacy against both major depressive disorder and depression due to bipolar disorder when administered via transdermal patches is scheduled to finish in September 2011.
• Due to its effectiveness against sea-sickness it has become commonly used by scuba divers.
• Scopolamine has been tested as a topical treatment for Aquagenic pruritus and was shown in several cases to be effective.

Recreational use

While it is occasionally used recreationally for its hallucinogenic properties, the experiences are often extremely mentally and physically unpleasant, and frequently physically dangerous; so repeated use is rare.

Use in interrogation

The effects of scopolamine were studied by criminologists in the early 20th century. In 2009, it was proven that Czechoslovak communist secret police used scopolamine at least three times to obtain confessions from alleged anti-state conspirators.

Criminal use and urban legends

In 1910, it was detected in the remains believed to be those of Cora Crippen, wife of Dr. Hawley Harvey Crippen, and was accepted at the time as the cause of her death since her husband was known to have bought some at the start of the year. Scopolamine poisoning is sometimes reported by the media as method by which people are raped, killed, or robbed, although some of these are unfounded rumors. For example, there have been rumors that robbers in the United States used a transcutaneous delivery mechanism involving business cards, pamphlets or flyers laced with the drug. The use of burundanga (aka scopolamine) impregnated credit cards to attack and to rob isolated people is often propagated by chain emails and some of these are reported as hoaxes or urban legends by specialized web sites.

Nevertheless, approximately one in five emergency room admissions for poisoning in Bogotá have been attributed to scopolamine. In June 2008, more than 20 people were hospitalized with psychosis in Norway after ingesting counterfeit Rohypnol tablets containing scopolamine.

There have also been reports of tourists being robbed after having scopolamine slipped into their food or drink. Recently, these incidents have been reported in Thailand.

In popular culture

• The fictional use of scopolamine as a truth serum is featured in a number of works including The House on 92nd Street; Farewell, My Lovely; Where Eagles Dare; Blood Hunt and The Guns of Navarone.
• In 1957, scopolamine 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." According to Dr. Liz Kingsley's film review site "And You Call Yourself a Scientist", Brandon's line "Prepare the scopolamine!" is "the only scientifically accurate line in the whole film."
• In Fear and Loathing In Las Vegas by Hunter S. Thompson, Dr. Gonzo mentions an incident in which he was given an entire datura root as a gift, ate the entire thing at once, and subsequently went blind, had to be taken back to his house in a wheelbarrow, and started making noises like a raccoon.
• In Carlos Castaneda's series of books The Teachings of Don Juan: A Yaqui Way of Knowledge, the datura plant is the least favored shamanic, revelatory drug of the titular character, however Castaneda shows an affinity for it. The book explores, in depth, Castaneda's alleged experiences under the influence of the drug, as well as the alleged rites surrounding its use and preparation.
• In Graham Greene's The Ministry of Fear, hyoscine is used by Rowe, the protagonist, to perform a mercy killing on his wife. Later in the book a man with infantile paralysis tries to poison him by putting hyoscine in his tea.
• Scopolamine and "Twilight Sleep" were integral to the plot of The X-Files season four episode Unruhe. The drug was used as an interrogation tool during Episode 9 of NBC's Kidnapped. It was also featured in "Smut", a December 2008 episode of Law & Order: Special Victims Unit's tenth season, in which a rapist used scopolamine to prevent the women he raped from resisting him and from forming memories.
• The drug was portrayed as a mind-controlling drug in Castle episode "Undead Again" to enhance the experience of playing a zombie. A victim was convinced that he actually was a zombie and should kill a man. Later, he fell into a deathlike trance.
• According to Janet Flanner (Genêt), in her 1972 book Paris was Yesterday (1925–1939), a collection of her New Yorker pieces, Prince Yussupoff was accused of poisoning with scopolamine the family of Princess Demidoff at regular tea parties in page 51 of the Penguin edition.