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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/11/25 22:06:37」(JST)

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Dicycloverine, also known as dicyclomine, is a prescription medication that relieves muscle spasms in the gastrointestinal tract through an apparent mechanism of nonselective smooth muscle relaxation, and that presents a range of anticholinergic side effects. It was first synthesized in the United States circa 1945.

Medical uses

A 10-mg oral capsule of dicyclomine hydrochloride, manufactured by Mylan

Dicyclomine is used to treat intestinal hypermotility,^{[citation needed]} and the symptoms of irritable bowel syndrome^[1] (also known as spastic colon^{[citation needed]}). It relieves muscle spasms in the gastrointestinal tract; while the mechanism or mechanisms of dicycloverine action were, as of 2004,^{[needs update]} unestablished, the drug "appears to act as nonselective smooth muscle relaxant."^[1] The drug presents adverse events that are "manifestations of pharmacologic effects at muscarinic-cholinergic receptors," events which are "usually... reversible when therapy is discontinued."^[1]

In the UK, it is an ingredient of a multiple-ingredient preparation, with an antiflatulent (simethicone) and two antacids, under the trade name Kolanticon.^{[citation needed]} In India, it is of a compound with paracetamol under the trade name Cyclopam.^{[citation needed]} It is also marketed as Meftal-SPAS containing mefenamic acid along with dicyclomine hydrochloride as an analgesic and antispasmodic.^{[citation needed]} Also it is a part of Normaxin containing two other salts clidinium bromide and chlordiazepoxide.^{[citation needed]}

Side effects

Dicycloverine can cause a range of anticholinergic side effects such as dry mouth, nausea,^[1] and, at higher doses, deliriant effects.^{[citation needed]} Recreational use of this drug for its anticholinergic effects (both low dose for euphoria and high dose for delirium) has been rarely reported.^{[citation needed]}

Precautions

Because dicycloverine is known to "impair mental alertness or physical coordination", those taking the drug should "avoid driving or operating machinery until effect on [the] individual are known".^[1] It is also important that women inform their clinicians "if they are or plan to become pregnant or plan to breast-feed".^[1]

Discovery

Chemical synthesis in discovery

Original cyclomine discovery synthesis.^[2]^{[non-primary source needed]}

Dicycloverine was first synthesized chemically in the United States circa 1945 (with patent from Wm S Merrell Company filed in January 1946, presentation at the September 1946 meeting of the Medicinal Chemistry Section of the A.C.S., and publication of the preparation in that Society's journal in November 1947).^[2]^[3]^{[non-primary source needed]}

The discovery synthesis came in the preparation of a family of aminoesters of 1-substituted cycloalkane-carboxylic acids, and proceeded for this specific compound (see scheme) via "condensation" (double alkylation) of phenylacetonitrile with 1,5-dibromopentane in the presence of sodamide (NaNH₂) dissolved in diethyl ether-liquid ammonia at low-temperature, which gave the 1,1-disubstituted cyclohexanenitrile. Alcoholysis of that nitrile in ethanol (EtOH) and sulfuric acid (H₂SO₄) gave the corresponding carboxylic acid ethyl ester, which was transesterified as its crude mixture in toluene or xylene with 2-(diethylamino)ethanol [a sodium (Na)-catalysed reaction]. Catalytic hydrogenation using hydrogen gas (H₂) over Adam's catalyst (PtO₂, abbreviated here PtO) in acetic acid reduced the aromatic ring of the original phenylacetonitrile the corresponding second cyclohexane ring,^[4] to give the final drug.^[2]^{[non-primary source needed]}

References

^ ^a ^b ^c ^d ^e ^f AHFS Staff (2006). "Dicyclomine hydrochloride". AHFS DI Essentials. Bethesda, MD: American Society of Health-System Pharmacists / drugs.com. Retrieved November 12, 2016.
^ ^a ^b ^c Tilford, C. H.; Van Campen, Jr., M. G.; Shelton, R. S. (1947). "Aminoesters of Substituted Alicylic Carboxylic Acids". Journal of the American Chemical Society. 69 (11): 2902–2906. doi:10.1021/ja01203a077.
^ US patent 2474796A, Van Campen, Jr., Marces George & Tilford, Charles Harmon, "Alkylaminoalkyl esters of alicyclyl-alicyclic carboxylic acids", published June 28, 1949, assigned to Wm S Merrell Co.
^ The generation of Adam's catalyst in this situation is inferred; see Norman, Richard O.C.; Coxon, James M. (1993). Principles of Organic Synthesis (3rd ed.). Boca Raton, FL: CRC Press. p. 631 and passim. ISBN 0748761624. The involvement of transfer hydrogenation is not ruled out by the primary source description.

External links

"Dicyclomine". Medicine Net.

UpToDate Contents

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1. 成人における過敏性腸症候群の治療 treatment of irritable bowel syndrome in adults
2. 炎症性腸疾患患者における過敏性腸症候群 irritable bowel syndrome in patients with inflammatory bowel disease
3. 小児や青年の機能性腹痛症：プライマリーケアでのマネージメント functional abdominal pain in children and adolescents management in primary care
4. 高齢者に対する薬剤処方 drug prescribing for older adults
5. アカラシアの治療の概要 overview of the treatment of achalasia

English Journal

Species Differences in the Antidiarrheal and Antispasmodic Activities of Lepidium sativum and Insight into Underlying Mechanisms.

Gilani AH, Rehman NU, Mehmood MH, Alkharfy KM.SourceNatural Product Research Unit, Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi, 74800, Pakistan; Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Phytotherapy research : PTR.Phytother Res.2013 Jul;27(7):1086-94. doi: 10.1002/ptr.4819. Epub 2012 Sep 25.
The aim of this study was to see if the crude extract of Lepidium sativum (Ls.Cr) exhibits species specificity in its antidiarrheal and antispasmodic activities along with insight into the underlying mechanisms using the in-vivo and in-vitro experiments. Ls.Cr inhibited castor oil-induced diarrhea i
PMID 23007892

Acetylcholine receptors regulate gene expression that is essential for primitive streak formation in murine embryoid bodies.

Arima N, Uchida Y, Yu R, Nakayama K, Nishina H.SourceDepartment of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Tokyo 113-8510, Japan.
Biochemical and biophysical research communications.Biochem Biophys Res Commun.2013 Jun 7;435(3):447-53. doi: 10.1016/j.bbrc.2013.05.006. Epub 2013 May 10.
Muscarinic acetylcholine receptors (mAchRs) are critical components of the cholinergic system, which is the key regulator of both the central and peripheral nervous systems in mammals. Interestingly, several components of the cholinergic system, including mAchRs and choline acetyltransferase (ChAT),
PMID 23665324

IL-6 attenuates trimethyltin-induced cognitive dysfunction via activation of JAK2/STAT3, M1 mAChR and ERK signaling network.

Kim BK, Tran HY, Shin EJ, Lee C, Chung YH, Jeong JH, Bach JH, Kim WK, Park DH, Saito K, Nabeshima T, Kim HC.SourceDepartment of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, South Korea.
Cellular signalling.Cell Signal.2013 Jun;25(6):1348-60. doi: 10.1016/j.cellsig.2013.02.017. Epub 2013 Mar 14.
We previously reported that interleukin (IL)-6 deficiency potentiates trimethyltin (TMT)-induced convulsive neurotoxicity. The purpose in this study was to investigate the molecular mechanism by which cytokines affect TMT-induced cognitive impairment. To accomplish this, we examined hippocampal chan
PMID 23499905

Japanese Journal

Experimental Analysis of Antimicrobial Action of Dicyclomine Hydrochloride

Biological & pharmaceutical bulletin 27(12), 2010-2013, 2004-12-01
NAID 110003665749

Chemically Modified Carbon Paste Electrode for the Potentiometric Determination of Dicylomine Hydrochloride in Batch and in FIA Conditions

Analytical Sciences 20(6), 911-916, 2004
NAID 130004440951

Role of 5-HT_<1A> Receptors in a Mouse Passive Avoidance Paradigm

The Japanese journal of pharmacology 84(4), 418-424, 2000-12-01
NAID 10008186694

Related Pictures

Dicyclomine; Dicycloverin Dicyclomine Oral : Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD Dicyclomine hydrochloride 20 mg side effects : Atorvastatina generico peru Mefenamic acid And Dicyclomine Tablets - Actiza Pharmaceutical | Pharmaceutical

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リンク元	「ジサイクロミン」
拡張検索	「dicyclomine hydrochloride」

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Dicycloverine
Clinical data
Trade names	Byclomine, Bentyl, Dibent, Di-Spaz, Dilomine
AHFS/Drugs.com	International Drug Names
MedlinePlus	a684007
Pregnancy; category	AU: B1; US: B (No risk in non-human studies); ;
ATC code	A03AA07 (WHO);
Legal status
Legal status	AU: S4 (Prescription only); CA: ℞-only; UK: POM (Prescription only); US: ℞-only;
Pharmacokinetic data
Protein binding	>99%
Biological half-life	5 h
Identifiers
	IUPAC name 2-(diethylamino)ethyl 1-cyclohexylcyclohexane-1-carboxylate;
CAS Number	77-19-0 ;
PubChem CID	3042;
IUPHAR/BPS	355;
DrugBank	DB00804 ;
ChemSpider	2934 ;
UNII	4KV4X8IF6V;
KEGG	D07820 ;
ChEBI	CHEBI:4514 ;
ChEMBL	CHEMBL1123 ;
ECHA InfoCard	100.000.919
Chemical and physical data
Formula	C19H35NO2
Molar mass	309.487 g/mol
3D model (JSmol)	Interactive image;
	SMILES O=C(OCCN(CC)CC)C1(CCCCC1)C2CCCCC2 ;
	InChI InChI=1S/C19H35NO2/c1-3-20(4-2)15-16-22-18(21)19(13-9-6-10-14-19)17-11-7-5-8-12-17/h17H,3-16H2,1-2H3 ; Key:CURUTKGFNZGFSE-UHFFFAOYSA-N ;
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英: dicyclomine
化: 塩酸ジサイクロミン dicyclomine hydrochloride
商: コランチル配合、レスポリックス配合、Antispas, Bentyl

「dicyclomine hydrochloride」

　　[★] ジサイクロミン dicyclomine。塩酸ジサイクロミン

[mono-1] ^ ^a ^b ^c ^d ^e ^f AHFS Staff (2006). "Dicyclomine hydrochloride". AHFS DI Essentials. Bethesda, MD: American Society of Health-System Pharmacists / drugs.com. Retrieved November 12, 2016.

[Tildford-2] Tilford, C. H.; Van Campen, Jr., M. G.; Shelton, R. S. (1947). "Aminoesters of Substituted Alicylic Carboxylic Acids". Journal of the American Chemical Society. 69 (11): 2902–2906. doi:10.1021/ja01203a077.

[3] US patent 2474796A, Van Campen, Jr., Marces George & Tilford, Charles Harmon, "Alkylaminoalkyl esters of alicyclyl-alicyclic carboxylic acids", published June 28, 1949, assigned to Wm S Merrell Co.

[4] The generation of Adam's catalyst in this situation is inferred; see Norman, Richard O.C.; Coxon, James M. (1993). Principles of Organic Synthesis (3rd ed.). Boca Raton, FL: CRC Press. p. 631 and passim. ISBN 0748761624. The involvement of transfer hydrogenation is not ruled out by the primary source description.

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dicyclomine