関: dimenhydrinate

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antihistamine and antiemetic (trade name Dramamine) used to treat motion sickness (同)Dramamine

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/08/21 20:39:04」(JST)

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Scopolamine (USAN), hyoscine (BAN) also known as levo-duboisine or burundanga,^[4] 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).^[5]^[6] Scopolamine exerts its effects by acting as a competitive antagonist at muscarinic acetylcholine receptors, specifically M1 receptors^{[citation needed]}; it is thus classified as an anticholinergic, antimuscarinic drug. (See the article on the parasympathetic nervous system for details of this physiology.)

Its use in medicine is relatively limited, with its chief uses being in the treatment of motion sickness and postoperative nausea and vomiting.^[2]^[7]^[8]

Scopolamine is named after the plant genus Scopolia.^[6] The name "hyoscine" is from the scientific name for henbane, Hyoscyamus niger.^[9] It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.^[10]

1 Medical use
2 Adverse effects
- 2.1 Overdose
3 Medication interactions
4 Biosynthesis in plants
5 History
6 Methods of administration
7 Use in pregnancy
8 Use in breastfeeding
9 Recreational use
10 Use in the elderly population
11 Scopolamine-related hospitalizations
12 Interrogation and criminal use
13 Research
- 13.1 Intravenous infusions
- 13.2 Oral scopolamine
14 References

Medical use

Scopolamine has a number of uses in medicine where it is used to treat:^[11]^[12]

Postoperative nausea and vomiting and sea sickness, leading to its use by scuba divers.^[13]^[14]
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

and is sometimes used as a premedication (especially to reduce respiratory tract secretions) to surgery, mostly commonly via injection.^[11]^[12]

Adverse effects

Adverse effect incidence:^[1]^[2]^[7]^[8]^[15]

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)
Bradycardia
Urticaria
Pruritus (itching)

Rare (<0.1% incidence) adverse effects include

Constipation
Urinary retention (being unable to urinate)
Hallucinations
Agitation
Confusion
Restlessness
Seizures

Unknown frequency adverse effects include

Anaphylactic shock
Anaphylactic reactions
Dyspnea (shortness of breath)
Rash
Erythema
Other hypersensitivity reactions
Blurred vision
Mydriasis (dilated pupils)
Drowsiness
Dizziness
Somnolence

Overdose

Physostigmine is an acetylcholinesterase inhibitor that readily crosses the blood-brain barrier, and has been used as an antidote to treat the CNS depression symptoms of scopolamine overdose.^[16] Other than this supportive treatment, gastric lavage and induced emesis (vomiting) are usually recommended as treatments for overdoses.^[15] The symptoms of overdose include:^[1]^[15]

Tachycardia
Arrhythmia
Blurred vision
Photophobia
Urinary retention
Drowsiness or paradoxical excitement which can present with hallucinations
Cheyne-Stokes respiration
Dry mouth
Skin reddening
Inhibition of gastrointestinal motility

Medication interactions

Due to interactions with metabolism of other drugs, scopolamine can cause significant unwanted side effects when taken with other medications. Specific attention should be paid to other medications in the same pharmacologic class as scopolamine, also known as anti-cholinergics. The following medications could potentially interact with the metabolism of scopolamine: analgesics/pain medications, ethanol, zolpidem, thiazide diuretics, buprenorphine, anti-cholinergic drugs such as tiotropium, etc.

Biosynthesis in plants

The steps of the biosynthesis of scopolamine are:

Ornithine decarboxylase (EC 4.1.1.17) decarboxylates L-ornithine to putrescine.
Putrescine N-methyltransferase (EC 2.1.1.53) methylates putrescine to N-methylputrescine.^[17]
Putrescine oxidase (EC 1.4.3.10) deaminates N-methylputrescine to 4-methylaminobutanal.
4-methylaminobutanal spontaneously ring-closes to N-methyl-pyrrolium cation.
Something (no enzyme has been found) condenses pyrrolium cation with acetoacetic acid yielding hygrine.
Hygrine rearranges to tropinone.^[17]
Tropinone reductase I (EC 1.1.1.206) converts tropinone to tropine.
Tropine condenses with phenyllactate (made from phenylalanine) to form littorine.
A cytochrome P450 classified as Cyp80F1^[18] oxidizes and rearranges littorine to hyoscyamine aldehyde.
6beta-hydroxyhyoscyamine epoxidase (EC 1.14.11.14) epoxidizes hyoscyamine to scopolamine.^[17]

History

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.^[19] 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.^[20] 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).

NASA is currently developing a nasal administration method. With a precise dosage, the NASA spray formulation has been shown to work faster and more reliably than the oral form.^[21]

Use in pregnancy

Scopolamine crosses the placenta and is a pregnancy Category C medication, meaning that risk to the fetus cannot be ruled out [Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women, or studies in women and animals are not available. Drugs should be given only if the potential benefits justify the potential risk to the fetus]. It may cause respiratory depression and/or neonatal hemorrhage when used during pregnancy and some animal studies did report adverse events. Transdermal scopolamine has been used as an adjunct to epidural anesthesia for cesarean delivery without adverse CNS effects on the newborn. Except when used prior to cesarean section, use during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus.

Use in breastfeeding

Scopolamine enters breast milk via secretion. Although no human studies exists to document the safety of scopolamine while nursing, the manufacturer recommends caution be used if scopolamine be administered to a nursing woman.^[22]

Recreational use

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.^[23]

Use in the elderly population

Scopolamine use in the elderly can increase the likelihood of experiencing adverse effects from the drug. This phenomenon is especially true of the elder population who are also concurrently on several other medications. Avoid scopolamine use in this age group due to potent anticholinergic adverse effects and uncertain effectiveness.^[24]

Scopolamine-related hospitalizations

About one in five emergency room admissions for poisoning in Bogotá, Colombia have been attributed to scopolamine.^[4] In June 2008, more than 20 people were hospitalized with psychosis in Norway after ingesting counterfeit Rohypnol tablets containing scopolamine.^[25]

Interrogation and criminal use

The effects of scopolamine were studied by criminologists in the early 20th century.^[26] 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.^[27] Because of a number of undesirable side effects, scopolamine was shortly disqualified as a truth serum.^[28]

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.^[29]

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."^[30]

Research

Scopolamine has been shown in multiple studies to be a potent antidepressant and anxiolytic medication. Two methods of administration have been studied. The first is in-patient sessions where the patients receive an intravenous infusion of a relatively large quantity of scopolamine during a session that lasts 1–2 hours. The patients are monitored during the infusion and released soon after as the effects wear-off quickly.^[31] The second route of administration is oral scopolamine in a pill.

Intravenous infusions

In research assessing intravenous infusions, scopolamine has been found to produce rapid and robust antidepressant effects in patients with major depressive disorder.^[32]

Oral scopolamine

Scopolamine has been studied for depression.^[33]

References

^ ^a ^b ^c ^d "Buscopan Tablets - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Boehringer Ingelheim Limited. 11 September 2013. Retrieved 22 October 2013.
^ ^a ^b ^c ^d ^e "BUSCOPAN Tablets and Ampoules BUSCOPAN FORTE Tablets". TGA eBusiness Services (BOEHRINGER INGELHEIM PTY LIMITED). 8 November 2010. Retrieved 22 October 2013.
^ Putcha, L.; Cintrón, N. M.; Tsui, J.; Vanderploeg, J. M.; Kramer, W. G. (1989). "Pharmacokinetics and Oral Bioavailability of Scopolamine in Normal Subjects". Pharmacology Research 6 (6): 481–485. doi:10.1023/A:1015916423156. PMID 2762223.
^ ^a ^b Uribe-Granja, Manuel; Moreno-López, Claudia L.; Zamora S., Adriana; Acosta, Pilar J. (September 2005). "Perfil epidemiológico de la intoxicación con burundanga en la clínica Uribe Cualla S. A. de Bogotá, D. C" (pdf). Acta Neurológica Colombiana (in Spanish) 21 (3): 197–201.
^ Muranaka, T.; Ohkawa, H.; Yamada, Y. (1993). "Continuous Production of Scopolamine by a Culture of Duboisia leichhardtii Hairy Root Clone in a Bioreactor System". Applied Microbiology and Biotechnology 40 (2–3): 219–223. doi:10.1007/BF00170370.
^ ^a ^b The Chambers Dictionary. Allied Publishers. 1998. pp. 788, 1480. ISBN 978-81-86062-25-8.
^ ^a ^b "TRANSDERM SCOP (scopalamine) patch, extended release [Baxter Healthcare Corporation]". DailyMed. Baxter Healthcare Corporation. April 2013. Retrieved 22 October 2013.
^ ^a ^b "DBL™ HYOSCINE INJECTION BP". TGA eBusiness Services. Hospira Australia Pty Ltd. 30 January 2012. Retrieved 22 October 2013.
^ Cattell, Henry Ware (1910). Lippincott's new medical dictionary: a vocabulary of the terms used in medicine, and the allied sciences, with their pronunciation, etymology, and signification, including much collateral information of a descriptive and encyclopedic character. Lippincott. p. 435. Retrieved 25 February 2012.
^ "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014.
^ ^a ^b Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. pp. 49, 266, 822, 823. ISBN 978-0-85711-084-8. edit
^ ^a ^b Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3. edit
^ Bitterman, N.; Eilender, E.; Melamed, Y. (1991). "Hyperbaric Oxygen and Scopolamine". Undersea Biomedical Research 18 (3): 167–174. PMID 1853467. Retrieved 2008-08-13.
^ Williams, T. H.; Wilkinson, A. R.; Davis, F. M.; Frampton, C. M. (1988). "Effects of Transcutaneous Scopolamine and Depth on Diver Performance". Undersea Biomedical Research 15 (2): 89–98. PMID 3363755.
^ ^a ^b ^c "Kwells 300 microgram tablets - Summary of Product Characteristics". electronic Medicines Compendium. Bayer plc. 7 January 2008. Retrieved 22 October 2013.
^ Clinical anesthesia (6th ed. ed.). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins. 2009. p. 346. ISBN 978-0-7817-8763-5.
^ ^a ^b ^c Ziegler, J.; Facchini, P. J. (2008). "Alkaloid Biosynthesis: Metabolism and Trafficking". Annual Review of Plant Biology 59 (1): 735–769. doi:10.1146/annurev.arplant.59.032607.092730. PMID 18251710.
^ Li, R.; Reed, D. W.; Liu, E.; Nowak, J.; Pelcher, L. E.; Page, J. E.; Covello, P. S. (2006). "Functional Genomic Analysis of Alkaloid Biosynthesis in Hyoscyamus niger Reveals a Cytochrome P450 Involved in Littorine Rearrangement". Chemistry & Biology 13 (5): 513–520. doi:10.1016/j.chembiol.2006.03.005. PMID 16720272.
^ White, P. F.; Tang, J.; Song, D. et al. (2007). "Transdermal Scopolamine: An Alternative to Ondansetron and Droperidol for the Prevention of Postoperative and Postdischarge Emetic Symptoms". Anesthesia and Analgesia 104 (1): 92–96. doi:10.1213/01.ane.0000250364.91567.72. PMID 17179250.
^ "Transderm Scop patch prescribing information".
^ "NASA Signs Agreement to Develop Nasal Spray for Motion Sickness".
^ Briggs (1994). Drugs in Pregnancy and Lactation. Baltimore, MD: Williams and Wilkins. pp. 777–778.
^ Freye, E. (2010). "Toxicity of Datura Stramonium". Pharmacology and Abuse of Cocaine, Amphetamines, Ecstasy and Related Designer Drugs. Netherlands: Springer. pp. 217–218. doi:10.1007/978-90-481-2448-0_34. ISBN 978-90-481-2447-3.
^ Flicker; Ferris (1992). "Hypersensitivity to scopolamine in the elderly.". Psychopharmacology (Berl) 107 (2-3): 437–441. doi:10.1007/bf02245172. PMID 1615141.
^ "Bilsykemedisin i falske rohypnol-tabletter". Aftenposten.no.
^ House, R. E. (September 1922). "The Use of Scopolamine in Criminology". Texas State Journal of Medicine 18: 256–263.
reprinted House, R. E. (1931). "The Use of Scopolamine in Criminology". American Journal of Police Science (Northwestern University) 2 (4): 328–336. doi:10.2307/1147361. JSTOR 1147361.
^ Gazdík, J.; Navara, L. (2009-08-08). "Svědek: Grebeníček vězně nejen mlátil, ale dával jim i drogy" [A witness: Grebeníček not only beat prisoners, he also administered drugs to them] (in Czech). iDnes. Retrieved 2009-08-10.
^ ""Truth" Drugs in Interrogation". Central Intelligence Agency. Retrieved 14 June 2012.
^ "The Trial of H.H. Crippen" ed. by Filson Young (Notable British Trials series, Hodge, 1920), p. xxvii; see also evidence, pp. 68-77.
^ https://www.osac.gov/Pages/ContentReportDetails.aspx?cid=12118 Colombia 2012 Crime and Safety Report: Cartagena
^ Frankel, E; Drevets, W; Luckenbaugh, D; Speer, A; Nugent, A; Zarate, C; Furey, M (June 2011). "Scopolamine as a fast-acting antidepressant agent in bipolar depression: A randomized placebo-controlled clinical trial". Bipolar disorders (Wiley-Blackwell) 13 (s1): 45. ISSN 1398-5647.
^ Martinowich, K; Jimenez, DV; Zarate, CA; Jr, Manji, HK (August 2013). "Rapid antidepressant effects: moving right along". Molecular Psychiatry 18 (8): 856–863. doi:10.1038/mp.2013.55. PMID 23689537.
^ Han, C; Pae, CU (January 2013). "Oral scopolamine augmentation for major depression". Expert Review of Neurotherapeutics 13 (1): 19–21. doi:10.1586/ern.12.150. PMID 23253388.

English Journal

Fixed combination of cinnarizine and dimenhydrinate in the prophylactic therapy of vestibular migraine: an observational study.

Teggi R1, Colombo B, Gatti O, Comi G, Bussi M.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology.Neurol Sci.2015 Jun 3. [Epub ahead of print]
Vestibular migraine (VM) is one of the most frequent causes of episodic vertigo, with a lifetime prevalence of 0.98 %. Prophylactic therapy includes calcium channel blockers, beta-blockers, antiepileptic drugs and antidepressants. We studied the association of cinnarizine 20 mg and dimenhydrinate
PMID 26037548

Development of normalized spectra manipulating spectrophotometric methods for simultaneous determination of Dimenhydrinate and Cinnarizine binary mixture.

Lamie NT1, Yehia AM2.
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.Spectrochim Acta A Mol Biomol Spectrosc.2015 May 27;150:142-150. doi: 10.1016/j.saa.2015.05.048. [Epub ahead of print]
Simultaneous determination of Dimenhydrinate (DIM) and Cinnarizine (CIN) binary mixture with simple procedures were applied. Three ratio manipulating spectrophotometric methods were proposed. Normalized spectrum was utilized as a divisor for simultaneous determination of both drugs with minimum mani
PMID 26037499

Comparative study of spectrophotometric methods manipulating ratio spectra: an application on pharmaceutical binary mixture of cinnarizine and dimenhydrinate.

Lamie NT1.
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.Spectrochim Acta A Mol Biomol Spectrosc.2015 Apr 15;141:193-201. doi: 10.1016/j.saa.2015.01.033. Epub 2015 Jan 28.
Four simple, specific, accurate and precise spectrophotometric methods are developed and validated for simultaneous determination of cinnarizine (CIN) and dimenhydrinate (DIM) in a binary mixture with overlapping spectra, without preliminary separation. The first method is dual wavelength spectropho
PMID 25677532

Japanese Journal

Growth and lactic acid production by Lactobacillus casei ssp. rhammonsus in batch and membrane bioreactor: influence of yeast extract and triptone enrichment.

OLMOS A.
Biotechnol. Lett. 19, 709-714, 1997
NAID 80009816903

「トリプトン」

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.	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
Pharmacokinetic data
Bioavailability	0.13-8% (Oral), 3% (Rectal)
Metabolism	Hepatic (liver)
Half-life	4.5 hours
Excretion	Renal
Identifiers
CAS number	51-34-3
ATC code	A04AD01 N05CM05, S01FA02
PubChem	CID 5184
IUPHAR ligand	330
DrugBank	DB00747
ChemSpider	10194106
UNII	DL48G20X8X
KEGG	D00138
ChEBI	CHEBI:16794
ChEMBL	CHEMBL1201024
Chemical data
Formula	C17H21NO4
Mol. mass	303.353 g/mol
	SMILES OC[C@H](c1ccccc1)C(=O)O[C@@H]2C[C@H]3N(C)[C@@H](C2)[C@@H]4O[C@H]34;
	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 ; Key:STECJAGHUSJQJN-FWXGHANASA-N ;
(what is this?) (verify)

　　[★]

英: triptone
関: ジメンヒドリナート

[EMCBut-1] "Buscopan Tablets - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Boehringer Ingelheim Limited. 11 September 2013. Retrieved 22 October 2013.

[TGAor-2] "BUSCOPAN Tablets and Ampoules BUSCOPAN FORTE Tablets". TGA eBusiness Services (BOEHRINGER INGELHEIM PTY LIMITED). 8 November 2010. Retrieved 22 October 2013.

[pmid2762223-3] Putcha, L.; Cintrón, N. M.; Tsui, J.; Vanderploeg, J. M.; Kramer, W. G. (1989). "Pharmacokinetics and Oral Bioavailability of Scopolamine in Normal Subjects". Pharmacology Research 6 (6): 481–485. doi:10.1023/A:1015916423156. PMID 2762223.

[Uribe_et_al_2005-4] Uribe-Granja, Manuel; Moreno-López, Claudia L.; Zamora S., Adriana; Acosta, Pilar J. (September 2005). "Perfil epidemiológico de la intoxicación con burundanga en la clínica Uribe Cualla S. A. de Bogotá, D. C" (pdf). Acta Neurológica Colombiana (in Spanish) 21 (3): 197–201.

[5] Muranaka, T.; Ohkawa, H.; Yamada, Y. (1993). "Continuous Production of Scopolamine by a Culture of Duboisia leichhardtii Hairy Root Clone in a Bioreactor System". Applied Microbiology and Biotechnology 40 (2–3): 219–223. doi:10.1007/BF00170370.

[Chambers-6] The Chambers Dictionary. Allied Publishers. 1998. pp. 788, 1480. ISBN 978-81-86062-25-8.

[DM-7] "TRANSDERM SCOP (scopalamine) patch, extended release [Baxter Healthcare Corporation]". DailyMed. Baxter Healthcare Corporation. April 2013. Retrieved 22 October 2013.

[TGAin-8] "DBL™ HYOSCINE INJECTION BP". TGA eBusiness Services. Hospira Australia Pty Ltd. 30 January 2012. Retrieved 22 October 2013.

[Cattell1910-9] Cattell, Henry Ware (1910). Lippincott's new medical dictionary: a vocabulary of the terms used in medicine, and the allied sciences, with their pronunciation, etymology, and signification, including much collateral information of a descriptive and encyclopedic character. Lippincott. p. 435. Retrieved 25 February 2012.

[10] "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014.

[BNF-11] Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. pp. 49, 266, 822, 823. ISBN 978-0-85711-084-8. edit

[AMH-12] Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3. edit

[pmid1853467-13] Bitterman, N.; Eilender, E.; Melamed, Y. (1991). "Hyperbaric Oxygen and Scopolamine". Undersea Biomedical Research 18 (3): 167–174. PMID 1853467. Retrieved 2008-08-13.

[pmid3363755-14] Williams, T. H.; Wilkinson, A. R.; Davis, F. M.; Frampton, C. M. (1988). "Effects of Transcutaneous Scopolamine and Depth on Diver Performance". Undersea Biomedical Research 15 (2): 89–98. PMID 3363755.

[EMChyd-15] "Kwells 300 microgram tablets - Summary of Product Characteristics". electronic Medicines Compendium. Bayer plc. 7 January 2008. Retrieved 22 October 2013.

[16] Clinical anesthesia (6th ed. ed.). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins. 2009. p. 346. ISBN 978-0-7817-8763-5.

[Ziegler2008-17] Ziegler, J.; Facchini, P. J. (2008). "Alkaloid Biosynthesis: Metabolism and Trafficking". Annual Review of Plant Biology 59 (1): 735–769. doi:10.1146/annurev.arplant.59.032607.092730. PMID 18251710.

[18] Li, R.; Reed, D. W.; Liu, E.; Nowak, J.; Pelcher, L. E.; Page, J. E.; Covello, P. S. (2006). "Functional Genomic Analysis of Alkaloid Biosynthesis in Hyoscyamus niger Reveals a Cytochrome P450 Involved in Littorine Rearrangement". Chemistry & Biology 13 (5): 513–520. doi:10.1016/j.chembiol.2006.03.005. PMID 16720272.

[White-19] White, P. F.; Tang, J.; Song, D. et al. (2007). "Transdermal Scopolamine: An Alternative to Ondansetron and Droperidol for the Prevention of Postoperative and Postdischarge Emetic Symptoms". Anesthesia and Analgesia 104 (1): 92–96. doi:10.1213/01.ane.0000250364.91567.72. PMID 17179250.

[20] "Transderm Scop patch prescribing information".

[21] "NASA Signs Agreement to Develop Nasal Spray for Motion Sickness".

[22] Briggs (1994). Drugs in Pregnancy and Lactation. Baltimore, MD: Williams and Wilkins. pp. 777–778.

[23] Freye, E. (2010). "Toxicity of Datura Stramonium". Pharmacology and Abuse of Cocaine, Amphetamines, Ecstasy and Related Designer Drugs. Netherlands: Springer. pp. 217–218. doi:10.1007/978-90-481-2448-0_34. ISBN 978-90-481-2447-3.

[24] Flicker; Ferris (1992). "Hypersensitivity to scopolamine in the elderly.". Psychopharmacology (Berl) 107 (2-3): 437–441. doi:10.1007/bf02245172. PMID 1615141.

[25] "Bilsykemedisin i falske rohypnol-tabletter". Aftenposten.no.

[26] House, R. E. (September 1922). "The Use of Scopolamine in Criminology". Texas State Journal of Medicine 18: 256–263.
reprinted House, R. E. (1931). "The Use of Scopolamine in Criminology". American Journal of Police Science (Northwestern University) 2 (4): 328–336. doi:10.2307/1147361. JSTOR 1147361.

[27] Gazdík, J.; Navara, L. (2009-08-08). "Svědek: Grebeníček vězně nejen mlátil, ale dával jim i drogy" [A witness: Grebeníček not only beat prisoners, he also administered drugs to them] (in Czech). iDnes. Retrieved 2009-08-10.

[28] ""Truth" Drugs in Interrogation". Central Intelligence Agency. Retrieved 14 June 2012.

[Crippen-29] "The Trial of H.H. Crippen" ed. by Filson Young (Notable British Trials series, Hodge, 1920), p. xxvii; see also evidence, pp. 68-77.

[30] ttps://www.osac.gov/Pages/ContentReportDetails.aspx?cid=12118 Colombia 2012 Crime and Safety Report: Cartagena

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[32] Martinowich, K; Jimenez, DV; Zarate, CA; Jr, Manji, HK (August 2013). "Rapid antidepressant effects: moving right along". Molecular Psychiatry 18 (8): 856–863. doi:10.1038/mp.2013.55. PMID 23689537.

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