|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|
|Pregnancy cat.||B2 (AU) C (US)|
|Legal status||Prescription Only (S4) (AU) ℞-only (CA) POM (UK) ℞-only (US)|
|Routes||transdermal, ocular, oral, subcutaneous, intravenous, sublingual, rectal, buccal transmucousal, intramuscular|
|Bioavailability||0.13-8% (Oral), 3% (Rectal)|
|ATC code||A04 N05, S01|
|Mol. mass||303.353 g/mol|
|(what is this?)|
Scopolamine (USAN), hyoscine (BAN) also known as levo-duboisine or burundanga, sold as Scopoderm, 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 (Datura), angel's trumpets (Brugmansia), and corkwood (Duboisia). Scopolamine exerts its effects by acting as a competitive antagonist at muscarinic acetylcholine receptors, specifically M1 receptors; it is thus classified as an anticholinergic, antimuscarinic drug. (See the article on the parasympathetic nervous system for details of this physiology.)
- Postoperative nausea and vomiting and sea sickness, leading to its use by scuba divers.
- Motion sickness (where it is often applied as a transdermal patch behind the ear)
- Gastrointestinal spasms
- Renal or biliary spasms
- Aid in GI radiology and endoscopy
- Irritable bowel syndrome (IBS)
- Clozapine-induced hypersalivation (drooling)
- Bowel colic
- Uncommon (0.1%-1% incidence) adverse effects include
- Dry mouth
- Dyshidrosis (reduced ability to sweat to cool off)
- Tachycardia (usually occurs at higher doses and is succeeded by bradycardia)
- Rare (<0.1% incidence) adverse effects include
- Urinary retention (being unable to urinate)
- Unknown frequency adverse effects include
- Anaphylactic shock
- Anaphylactic reactions
- Dyspnea (shortness of breath)
- Other hypersensitivity reactions
- Blurred vision
Physostigmine is an acetylcholinesterase inhibitor that readily crosses the blood-brain barrier, and has been used to treat the CNS depression symptoms of scopolamine overdose. Other than this supportive treatment, gastric lavage and induced emesis (vomiting) are usually recommended as treatments for overdoses. The symptoms of overdose include:
- Blurred vision
- Urinary retention
- Drowsiness or paradoxical excitement which can present with hallucinations
- Cheyne-Stokes respiration
- Dry mouth
- Skin reddening
- Inhibition of gastrointestinal motility
Biosynthesis in plants
The biosynthesis of scopolamine begins with the decarboxylation of L-ornithine to putrescine by ornithine decarboxylase (EC 126.96.36.199). Putrescine is methylated to N-methylputrescine by putrescine N-methyltransferase (EC 188.8.131.52).
A putrescine oxidase (EC 184.108.40.206) 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.
Subsequently, tropinone reductase I (EC 220.127.116.11) 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 catalyzed by 6beta-hydroxyhyoscyamine epoxidase (EC 18.104.22.168) yielding scopolamine.
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, 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 of and methods for total synthesis of scopolamine and/or 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 Dolatin and Demerol amongst many other trade names.
Scopolamine was used in conjunction with morphine, oxycodone, or other opioids from before 1900 into the 1960s to put mothers in labor into a kind of "twilight sleep". The analgesia from scopolamine plus a strong opioid is deep enough to allow higher doses to be used as a form of anaesthesia.
Scopolamine mixed with oxycodone (Eukodal) and ephedrine was marketed by Merck as SEE (from the German initials of the ingredients) and Scophedal starting in 1928, and the mixture is sometimes mixed on site on rare occasions in the area of its greatest historical usage, namely Germany and Central Europe.
Scopolamine was also one of the active ingredients in Asthmador, an over-the-counter (OTC) smoking preparation marketed in the 1950s and '60s claiming to combat asthma and bronchitis. In November 1990, the US Food and Drug Administration forced OTC products with scopolamine and several hundred other ingredients that had allegedly not been proved effective off the market. Scopolamine shared a small segment of the OTC sleeping pill market with diphenhydramine, phenyltoloxamine, pyrilamine, doxylamine, and other first-generation antihistamines, many of which are still used for this purpose in drugs such as Sominex, Tylenol PM, NyQuil, etc.
Methods of administration
Scopolamine can be administered orally, subcutaneously, ophthalmically 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 three days. The oral, ophthalmic, and intravenous forms have shorter half-lives and are usually found in the form scopolamine hydrobromide (for example in Scopace, soluble 0.4 mg tablets or Donnatal).
While it is occasionally used recreationally for its hallucinogenic properties, the experiences are often mentally and physically extremely unpleasant, and frequently physically dangerous, so repeated use is rare.
About one in five emergency room admissions for poisoning in Bogotá, Colombia, 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.
Use in interrogation
The effects of scopolamine were studied by criminologists in the early 20th century. In 2009, it was proved that Czechoslovak communist State Security secret police used scopolamine at least three times to obtain confessions from alleged anti-state conspirators. Because of a number of undesirable side effects, scopolamine was shortly disqualified as a truth serum.
In 1910, scopolamine 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.
In 2008, Vice News aired an episode called Colombian Devil's Breath recounting the use of scopolamine by Colombian criminals as a suggestion drug. The two-part investigation contains multiple first-hand accounts of its use.
Scopolamine is used criminally as a date rape drug in Drug facilitated sexual assaults and as an aid to robbery,[dead link] the most common act being the clandestine drugging of a victim's drink.
Per the United States State Department (March 4, 2012): "One common and particularly dangerous method that criminals use in order to rob a victim is through the use of drugs. The most common 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. To avoid becoming a victim of scopolamine, one should never accept food or beverages offered by strangers or new acquaintances or leave food or beverages unattended. Victims of scopolamine or other drugs should seek immediate medical attention."
Hyoscine has been found to produce rapid and robust antidepressant effects in patients with major depressive disorder and bipolar depression when intravenously infused. There seems to be a gender discrepancy favouring women for antidepressant and anxiolytic response over men.
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