関: atropine、atropine sulfate、hyoscyamine methylbromide, Donnatal

WordNet

a poisonous crystalline alkaloid (isometric with atropine but more potent); used to treat excess motility of the gastrointestinal tract
a poisonous crystalline alkaloid extracted from the nightshade family; used as an antispasmodic and to dilate the eye pupil; also administered in large amounts as an antidote for organophosphate nerve agents or organophosphate insecticides

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/02/05 16:54:32」(JST)

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Hyoscyamine (also known as daturine) is a tropane alkaloid. It is a secondary metabolite found in certain plants of the Solanaceae family, including henbane (Hyoscyamus niger), mandrake (Mandragora officinarum), jimsonweed (Datura stramonium), tomato (Solanum lycopersicum) and deadly nightshade (Atropa belladonna). It is the levorotary isomer of atropine (third of the three major nightshade alkaloids) and thus sometimes known as levo-atropine. Hyoscyamine should not be confused with hyoscine, an older alternate name for the related nightshade-derived anticholinergic scopolamine for which it is the precursor.

Brand names for hyoscyamine include Symax, HyoMax, Anaspaz, Egazil, Buwecon, Cystospaz, Levsin, Levbid, Levsinex, Donnamar, NuLev, Spacol T/S and Neoquess.

Pharmacology

Hyoscyamine is an antagonist of muscarinic acetylcholine receptors (antimuscarinic). It blocks the action of acetylcholine at parasympathetic sites in sweat glands, salivary glands, stomach secretions, heart muscle, sinoatrial node, smooth muscle in the gastrointestinal tract, and the central nervous system. It increases cardiac output and heart rate, lowers blood pressure, dries secretions.^[1] It may antagonize serotonin.^[2] At comparable doses, hyoscyamine has 98 per cent of the anticholinergic power of atropine. The other major belladonna-derived drug scopolamine has 92 per cent of the antimuscarinic potency of atropine.^[2]

Biosynthesis in plants

Hyoscyamine can be extracted from plants of the Solanaceae family, notably Datura stramonium. As hyoscyamine is a direct precursor in the plant biosynthesis of scopolamine, it is produced via the same metabolic pathway.^[3]

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).^[4]

A putrescine oxidase (EC 1.4.3.10) 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 enzmyatic activity could be demonstrated that catalyzes this reaction. Hygrine further rearranges to tropinone.^[4]

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^[5] oxidizes and rearranges littorine to hyoscyamine aldehyde.

Uses

Hyoscyamine is used to provide symptomatic relief to various gastrointestinal disorders including spasms, peptic ulcers, irritable bowel syndrome, diverticulitis, pancreatitis, colic and cystitis. It has also been used to relieve some heart problems, control some of the symptoms of Parkinson's disease, as well as for control of respiratory secretions in palliative care.^[6] It may be useful in pain control for neuropathic pain treated with opioids as it increases the level of analgesia obtained. Several mechanisms are thought to contribute to this effect. The closely related drugs atropine and scopolamine and other members of the anticholinergic drug group like cyclobenzaprine, trihexyphenidyl, and orphenadrine are also used for this purpose. When hyoscyamine is used along with opioids or other anti-peristaltic agents, measures to prevent constipation are especially important given the risk of paralytic ileus.

Side effects

Side effects include dry mouth and throat, eye pain, blurred vision, restlessness, dizziness, arrhythmia, flushing, and faintness. An overdose will cause headache, nausea, vomiting, and central nervous system symptoms including disorientation, hallucinations, euphoria, sexual arousal, short-term memory loss, and possible coma in extreme cases. The euphoric and sexual effects are stronger than those of atropine but weaker than those of scopolamine, as well as dicycloverine, orphenadrine, cyclobenzaprine, trihexyphenidyl, and ethanolamine antihistamines like phenyltoloxamine.^{[citation needed]}

References

^ Edwards Pharmaceuticals, Inc.; Belcher Pharmaceuticals, Inc. (May 2010), DailyMed, U.S. National Library of Medicine, retrieved January 13, 2013
^ ^a ^b Kapoor, A. K.; Raju, S. M. (2013). Illustrated Medical Pharmacology. JP Medical Ltd. p. 131. ISBN 9789350906552. Retrieved January 11, 2014.
^ Ziegler, J; Facchini, PJ (2008). "Alkaloid biosynthesis: metabolism and trafficking.". Annual review of plant biology 59: 735–69. doi:10.1146/annurev.arplant.59.032607.092730. PMID 18251710.
^ ^a ^b 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.
^ http://www.nlm.nih.gov/medlineplus/druginfo/meds/a684010.html

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Cardioprotection by acetylcholine: A novel mechanism via mitochondrial biogenesis and function involving the PGC-1α pathway.

Sun L, Zhao M, Yu XJ, Wang H, He X, Liu JK, Zang WJ.SourceDepartment of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Journal of cellular physiology.J Cell Physiol.2013 Jun;228(6):1238-48. doi: 10.1002/jcp.24277.
Mitochondrial biogenesis disorders appear to play an essential role in cardiac dysfunction. Acetylcholine as a potential pharmacologic agent exerts cardioprotective effects. However, its direct action on mitochondria biogenesis in acute cardiac damage due to ischemia/reperfusion remains unclear. The
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Vagal stimulation triggers peripheral vascular protection through the cholinergic anti-inflammatory pathway in a rat model of myocardial ischemia/reperfusion.

Zhao M, He X, Bi XY, Yu XJ, Gil Wier W, Zang WJ.SourceDepartment of Pharmacology, College of Medicine, Xi'an Jiaotong University, No. 76 Yanta West Road, P.O. Box 77#, Xi'an, 710061, People's Republic of China.
Basic research in cardiology.Basic Res Cardiol.2013 May;108(3):345. doi: 10.1007/s00395-013-0345-1. Epub 2013 Mar 22.
Myocardial ischemia/reperfusion (I/R) induces inflammatory response that may lead to remote vascular injury. Vagal nerve elicits the cholinergic anti-inflammatory pathway by activating α7 nicotinic acetylcholine receptors (α7nAChR). Nevertheless, the role of vagal nerve-mediated anti-inflammatory
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Is behavioral sensitization to 3,4-methylenedioxymethamphetamine (MDMA) mediated in part by cholinergic receptors?

Lettfuss NY, Seeger-Armbruster S, von Ameln-Mayerhofer A.SourceDepartment of Neuropharmacology, Institute of Neurobiology, University of Tuebingen, Auf der Morgenstelle 28E, 72076 Tuebingen, Germany. Electronic address: nlettfuss@aol.com.
Behavioural brain research.Behav Brain Res.2013 May 1;244:116-9. doi: 10.1016/j.bbr.2013.01.033. Epub 2013 Feb 1.
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Japanese Journal

LC/MS/MSによるヒト血清・尿中のヒヨスチアミンおよびスコポラミンの分析

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LC/MS/MSによるヒト血清・尿中のヒヨスチアミンおよびスコポラミンの分析法について検討した．LC条件はODSカラムを用いて移動相に陽イオン分析用イオンペア試薬であるIPCC-MS3を添加し水-メタノール系でグラジエント分析した．イオン化はエレクトロスプレーイオン化ポジティブモードで行った．試料の前処理にはOasis HLBカートリッジおよびPSAカートリッジを用いた．血清・尿にヒヨスチアミンお …
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Root tip-dependent, active riboflavin secretion by Hyoscyamus albus hairy roots under iron deficiency

Higa Ataru,Miyamoto Erika,Rahman Laiq ur,Kitamura Yoshie
Plant Physiology and Biochemistry 46(4), 452-460, 2008-04-04
Hyoscyamus albus hairy roots with/without an exogenous gene (11 clones) were established by inoculation of Agrobacterium rhizogenes. All clones cultured under iron deficient condition secreted ribofla …
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チョウセンアサガオに接木したナスによる食中毒事例

大城直雅,國吉和昌,中村章弘,新城安哲,玉那覇康二,稲福恭雄
食品衛生学雑誌 49(5), 376-379, 2008
家庭菜園で栽培したナスの入ったスパゲティーミートソースを摂食した夫婦が，ふらつき，ろれつがまわらない，意識混濁などの症状を呈し，相次いで救急診療を受診した．このナスはチョウセンアサガオに接木したもので，食品残品と患者血清からスコポラミンとアトロピンが検出された．本事例は沖縄県初のチョウセンアサガオ関連食中毒事例であり，接木による食中毒事例は本邦初の報告と思われる．
NAID 130000671603

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★リンクテーブル★

リンク元	「ヒヨスチアミン」「ヒヨスシアミン」
拡張検索	「hyoscyamine methylbromide」

「ヒヨスチアミン」

Hyoscyamine
Systematic (IUPAC) name
	(S)-(1R,3r,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl 3-hydroxy-2-phenylpropanoate
Clinical data
Trade names	Anaspaz, Levbid, Levsin
AHFS/Drugs.com	monograph
MedlinePlus	a684010
Pregnancy; category	C;
Legal status	AU: Prescription Only (S4); US: Prescription only;
Routes	Oral, Injection
Pharmacokinetic data
Bioavailability	50% Protein binding
Metabolism	Hepatic
Half-life	3–5 hrs.
Excretion	Urine
Identifiers
CAS number	101-31-5
ATC code	A03BA03
PubChem	CID 154417
DrugBank	DB00424
ChemSpider	10246417
UNII	PX44XO846X
ChEBI	CHEBI:17486
ChEMBL	CHEMBL1697729
Chemical data
Formula	C17H23NO3
Molecular mass	289.375 g/mol
	SMILES CN3[C@H]1CC[C@@H]3C[C@@H](C1)OC(=O)[C@H](CO)c2ccccc2;
	InChI InChI=1S/C17H23NO3/c1-18-13-7-8-14(18)10-15(9-13)21-17(20)16(11-19)12-5-3-2-4-6-12/h2-6,13-16,19H,7-11H2,1H3/t13-,14+,15+,16-/m1/s1 ; Key:RKUNBYITZUJHSG-FXUDXRNXSA-N ;
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