scopolamine scopolamine scopolamine, also known as hyoscine, or devil's breath, is a natural or synthetically produced tropane alkaloid and anticholinergic drug that is used as a medication 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. its duration of action for oral administration is less well-studied, and may often be confounded by other factors but based on preliminary or circumstantial observations it can be deduced as lasting around 8 hours, but possibly even up to 18 hours or longer depending on the dosage. scopolamineclinical datatrade namestransdermscop, kwells, othersother namesscopolamine, hyoscine hydrobromide, scopolamine hydrobromideahfs/drugs.commonographmedlineplusa682509license data us dailymed: scopolamine pregnancycategory au: b2 routes ofadministrationby mouth, transdermal, ophthalmic, subcutaneous, intravenous, sublingual, rectal, buccal, transmucosal, intramusculardrug class antimuscarinic deliriant antiemetic amnestic atc codea04ad01 (who) n05cm05 (who), s01fa02 (who)legal statuslegal status au: s4 (prescription only) / s2 uk: pom (prescription only) / p us: ℞-only pharmacokinetic datametabolismliverelimination half-life4.5 hoursexcretionkidneyidentifiers iupac name (–)-(s)-3-hydroxy-2-phenylpropionic acid (1r,2r,4s,5s,7α,9s)-9-methyl-3-oxa-9-azatricyclonon-7-yl ester cas number51-34-3 ypubchem cid5184iuphar/bps330drugbankdb00747 ychemspider10194106 yuniidl48g20x8xkeggd00138 yas salt: d02071 ychebichebi:16794 ychemblchembl569713 ncomptox dashboard (epa)dtxsid6023573 echa infocard100.000.083 chemical and physical dataformulac17h21no4molar mass303.358 g·mol−13d model (jsmol)interactive image smiles oc(c1ccccc1)c(=o)o2c3n(c)(c2)4o34 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 ykey:stecjaghusjqjn-fwxghanasa-n y ny (what is this?) (verify) scopolamine is in the antimuscarinic family of drugs and works by blocking some of the effects of acetylcholine within the nervous system. 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, criminal 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. it is on the world health organization's list of essential medicines. medical uses scopolamine has a number of formal uses in modern medicine where it is used in its isolated form, and in low doses to treat: postoperative nausea and vomiting. motion sickness, including sea sickness, leading to its use by scuba divers (where it is often applied as a transdermal patch behind the ear). such drugs taken to relieve typical symptoms of motion sickness (including nausea, dizziness, etc.) contain compounds that may exacerbate drowsiness, especially if not dosed modestly or within their therapeutic windows. additionally, scopolamine has also proven to be clinically effective for palliatively treating more obscure forms of motion sickness, such as the poorly understood sopite syndrome; which can change mood, cognitive functions and a sufferer's overall sense of well-being in a more profound way than the stereotypical symptoms of motion sickness like nausea and vertigo. antihistamines are commonly used to treat motion sickness; however, side effects often include drowsiness and impaired cognitive abilities. anticholinergics such as scopolamine, despite showing effectiveness against the more uncomfortable, nauseating and disorienting aspects of motion sickness disorders, it may still induce its own form of drowsiness, or type of intoxicating narcotic-like sedation, rather than that of the true pathological fatigue associated with the syndrome itself. gastrointestinal spasms renal or biliary spasms aid in gastrointestinal radiology and endoscopy irritable bowel syndrome clozapine-induced drooling bowel colic eye inflammation it is sometimes used as a premedication, (especially to reduce respiratory tract secretions) in surgery, most commonly by injection. common side effects include sleepiness, blurred vision, dilated pupils, and dry mouth. it is not recommended in people with angle-closure glaucoma or bowel obstruction. whether its use during pregnancy is safe remains unclear, and use during breastfeeding is still cautioned by health professionals and manufacturers of the drug. breastfeeding scopolamine enters breast milk by secretion. although no human studies exist to document the safety of scopolamine while nursing, the manufacturer recommends that caution be taken if scopolamine is administered to a breastfeeding woman. elderly the likelihood of experiencing adverse effects from scopolamine is increased in the elderly, relative to younger people. this phenomenon is especially true for older people who are also on several other medications. scopolamine use should be avoided in this age group because of these potent anticholinergic adverse effects, which have also been linked to an increased risk for dementia. adverse effects adverse effect incidence: uncommon (0.1–1% incidence) adverse effects include: dry mouth anhidrosis (reduced ability to sweat to cool off) tachycardia (usually occurs at higher doses and is succeeded by bradycardia) bradycardia urticaria (hives) pruritus (itching) rare (<0.1% incidence) adverse effects include: constipation urinary retention hallucinations agitation confusion akathisia restlessness seizures unknown frequency adverse effects include: anaphylactic shock or reactions dyspnea (shortness of breath) rash erythema other hypersensitivity reactions blurred vision mydriasis (dilated pupils) drowsiness dizziness somnolence overdose physostigmine, a cholinergic drug that readily crosses the blood–brain barrier, has been used as an antidote to treat the central nervous system depression symptoms of a scopolamine overdose. other than this supportive treatment, gastric lavage and induced emesis (vomiting) are usually recommended as treatments for oral overdoses. the symptoms of overdose include: tachycardia arrhythmia blurred vision photophobia urinary retention drowsiness or paradoxical reaction, which can present with hallucinations cheyne-stokes respiration dry mouth skin reddening inhibition of gastrointestinal motility interactions due to scopolamine's notable effects on the central and peripheral nervous systems, as well as its presumed metabolic interactions with the biological effects of other drugs, scopolamine can cause significant unwanted side effects or unpredictable synergies when taken with other medications or compounds. specific attention should be paid to other medications in the same pharmacologic class as scopolamine, also known as anticholinergics. these additional compounds could also potentially interact with the metabolism of scopolamine: receptor-binding analgesic/pain medication such as gabapentinoids or opioids, ethanol, cannabinoids, zolpidem, thiazide diuretics, nicotine, caffeine, benzodiazepines, buprenorphine, and especially anticholinergic drugs such as tiotropium, diphenhydramine, dimenhydrinate, etc. nicotine and caffeine in particular likely have a counteracting effect on the effects of scopolamine due to their opposing effect on acetylcholine signaling. cns stimulants in general may interact dangerously with scopolamine due to possible cumulative cardiotoxicity, especially with amphetamines or cocaine; with the latter being a tropane alkaloid like scopolamine. co-administration of modafinil and scopolamine however has been used in studying the treatment of sopite syndrome; an atypical type of motion sickness that brings about increased nausea and vertigo as well as fatigue during long periods of movement. although scopolamine has been shown to treat many of its symptoms, it can also contribute to or worsen the drowsiness aspect which was the reason for testing its use in conjunction with a stimulant like modafinil, which appears to be effective when taken in combination with anticholinergics while lacking the side effects of other stimulants. route of administration scopolamine can be taken by mouth, subcutaneously, in the eye, and intravenously, as well as via a transdermal patch. pharmacokinetic scopolamine undergoes first-pass metabolism and about 2.6% is excreted unchanged in urine. grapefruit juice decreases metabolism of scopolamine, consequently increasing plasma concentration. 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. in doses higher than intended for medicinal use; the hallucinogenic alteration of consciousness, as well as the deliriousness 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 only associated with the antagonism of postsynaptic m1 receptors and currently other receptor subtypes have not been implicated. 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. although often broadly referred to as simply being 'anticholinergic', antimuscarinic would be more specified and accurate terminology to use for scopolamine, as for instance it is not known to block nicotinic receptors. biosynthesis in plants scopolamine is among the secondary metabolites of plants from solanaceae (nightshade) family of plants, such as henbane (hyoscyamus niger), jimson weed (datura), angel's trumpets (brugmansia), deadly nightshade (belladonna), mandrake (mandragora officinarum), and corkwood (duboisia). biochemistry of tropane class compounds. hyoscyamine and scopolamine are present and labeled. the biosynthesis of scopolamine begins with the decarboxylation of l-ornithine to putrescine by ornithine decarboxylase. putrescine is methylated to n-methylputrescine by putrescine n-methyltransferase. a putrescine oxidase 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 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 yielding scopolamine. 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. following the description of the structure and activity of scopolamine by ladenburg, the search for synthetic analogues, and methods for total synthesis, of scopolamine and 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 dolantin and demerol amongst many other trade names. in 1899, a dr. 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 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. society and culture 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. 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. recreational and religious use while it has been occasionally used recreationally for its hallucinogenic properties, the experiences are often unpleasant, mentally and physically. it is also physically dangerous and officially classified as a deliriant drug,