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Carbachol (Carbastat, Carboptic, Isopto Carbachol, Miostat), also known as carbamylcholine, is a cholinomimetic drug that binds and activates the acetylcholine receptor. Thus it is classified as a cholinergic agonist. It is primarily used for various ophthalmic purposes, such as for treating glaucoma, or for use during ophthalmic surgery. It is generally administered as an ophthalmic solution (i.e. eyedrops).

Carbachol produces effects comparable to those of V-series nerve agents if a massive overdose is administered (as may occur following industrial and shipping accidents) and therefor constitutes a risk to human health. It is classified as an extremely hazardous substance in the United States as defined in Section 302 of the U.S. Emergency Planning and Community Right-to-Know Act (42 U.S.C. 11002), and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.^[1]

Chemistry and pharmacology

Carbachol is a choline carbamate and a positively charged quaternary ammonium compound.^[2] It is not well absorbed in the gastro-intestinal tract and does not cross the blood–brain barrier. It is usually administered topical ocular or through intraocular injection.^[2] Carbachol is not easily metabolized by cholinesterase, it has a two to 5 minute onset of action and its duration of action is 4 to 8 hours with topical administration and 24 hours for intraocular administration. Since carbachol is poorly absorbed through topical administration, benzalkonium chloride is mixed in to promote absorption.^[2]

Carbachol is a parasympathomimetic that stimulates both muscarinic and nicotinic receptors.^[2] In topical ocular and intraocular administration its principal effects are miosis and increased aqueous humour outflow.^[2]

In the cat and rat, carbachol is well known for its ability to induce rapid eye movement (REM) sleep when microinjected into the pontine reticular formation. Carbachol elicits this REM sleep-like state via activation of postsynaptic muscarinic cholinergic receptors (mAChRs).^[2]

A recent review indicates that carbachol is a strong promoter of ICC activity, which is mediated through the calcium-activated chloride channel, anoctamin 1.^[3]

Indications

Carbachol is primarily used in the treatment of glaucoma, but it is also used during ophthalmic surgery.^[2] Carbachol eyedrops are used to decrease the pressure in the eye for people with glaucoma. It is sometimes used to constrict the pupils during cataract surgery.

Topical ocular administration is used to decrease intraocular pressure in people with primary open-angle glaucoma. Intraocular administration is used to produce miosis after lens implantation during cataract surgery. Carbachol can also be used to stimulate bladder emptying if the normal emptying mechanism is not working properly.

In most countries carbachol is only available by prescription. Outside the United States, it is also indicated for urinary retention as an oral (2 mg) tablet.^[2]^[4]

Contraindications

Use of carbachol, as well as all other muscarinic receptor agonists, is contraindicated in patients with asthma, coronary insufficiency, gastroduodenal ulcers, and incontinence. The parasympathomimetic action of this drug will exacerbate the symptoms of these disorders.

Overdose

The effects of a systemic overdose will probably be similar to the effects of a nerve agent (they both act on the cholinergic system, increasing cholinergic transmission), but its toxicity is much weaker and it is easier to antagonize in overdose. When administered ocularly there is little risk of such effects, since the doses are much smaller (see topical versus systemic administration).^[5]

References

^ "40 C.F.R.: Appendix A to Part 355—The List of Extremely Hazardous Substances and Their Threshold Planning Quantities" (PDF) (July 1, 2008 ed.). Government Printing Office. Retrieved October 29, 2011.
^ ^a ^b ^c ^d ^e ^f ^g ^h "Carbachol". PubChem Compound. Retrieved 6 March 2014.
^ Sanders KM, Zhu MH, Britton F, Koh SD, Ward SM (February 2012). "Anoctamins and gastrointestinal smooth muscle excitability". Exp. Physiol. 97 (2): 200–206. doi:10.1113/expphysiol.2011.058248. PMC 3272164. PMID 22002868.
^ "Carbachol generics". ndrugs. Retrieved 6 March 2014.
^ Richard A. Harvey; Pamela C. Champe, eds. (2009). Lippincott's Illustrated Review: Pharmacology (4th ed.). Lippincott Williams & Wilkins. p. 49. ISBN 978-0781771559.

External links

RxList.com - Carbachol
International Carbachol brands and dosage forms
PMC overdose case reports (humans)

UpToDate Contents

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English Journal

The Cholinergic Signaling Responsible for the Expression of a Memory-Related Protein in Primary Rat Cortical Neurons.

Chen TJ1, Chen SS2, Wang DC3, Hung HS1.
Journal of cellular physiology.J Cell Physiol.2016 Nov;231(11):2428-38. doi: 10.1002/jcp.25347. Epub 2016 Mar 8.
Cholinergic dysfunction in the brain is closely related to cognitive impairment including memory loss. In addition to the degeneration of basal forebrain cholinergic neurons, deficits in the cholinergic receptor signaling may also play an important role. In the present study, to examine the choliner
PMID 26895748

Cholinergic and glutamatergic transmission at synapses between pedunculopotine tegmental nucleus axonal terminals and A7 catecholamine cell group noradrenergic neurons in the rat.

Li MJ1, Chang TW1, Hung WC1, Wu CY1, Luo YC1, Chang TH2, Lin C3, Yang CS4, Yang HW5, Min MY6.
Neuropharmacology.Neuropharmacology.2016 Nov;110(Pt A):237-50. doi: 10.1016/j.neuropharm.2016.07.011. Epub 2016 Jul 14.
We characterized transmission from the pedunculopotine tegmental nucleus (PPTg), which contains cholinergic and glutamatergic neurons, at synapses with noradrenergic (NAergic) A7 neurons. Injection of an anterograde neuronal tracer, biotinylated-dextran amine, into the PPTg resulted in labeling of a
PMID 27422407

Chronic treatment with resveratrol improves overactive bladder in obese mice via antioxidant activity.

Alexandre EC1, Calmasini FB1, de Oliveira MG1, Silva FH2, da Silva CP3, André DM1, Leonardo FC2, Delbin MA3, Antunes E4.
European journal of pharmacology.Eur J Pharmacol.2016 Oct 5;788:29-36. doi: 10.1016/j.ejphar.2016.06.017. Epub 2016 Jun 15.
The objective of the present work was to evaluate whether oral intake with resveratrol ameliorates overactive bladder in high-fat fed mice. Male C57BL6 mice fed with standard chow or high-fat diet to induce obesity received a two-week therapy with resveratrol (100mg/kg, given as a daily gavage). Wei
PMID 27316789

Japanese Journal

Critical role of cholinergic transmission from the laterodorsal tegmental nucleus to the ventral tegmental area in cocaine-induced place preference

Shinohara Fumiya,Kihara Yukari,Ide Soichiro,Minami Masabumi,Kaneda Katsuyuki
Neuropharmacology 79, 573-579, 2014-04
… Intra-LDT injection of carbachol, which hyperpolarizes LDT neurons, and of NMDA and AMPA receptor antagonists before cocaine conditioning blocked and attenuated cocaine CPP, respectively, indicating the necessity of LDT activity for acquiring the CPP. …
NAID 120005367413

カルバコール誘導β振動によるてんかん波抑制 (ニューロコンピューティング)

澤田豊宏,夏目季代久
電子情報通信学会技術研究報告 = IEICE technical report : 信学技報 113(382), 105-110, 2014-01-20
NAID 40019982409

Muscarinic Receptor Binding of the Novel Radioligand, [3H]Imidafenacin in the Human Bladder and Parotid Gland

Yoshida Akira,Kuraoka Shiori,Ito Yoshihiko,Okura Takashi,Deguchi Yoshiharu,Otsuka Atsushi,Ozono Seiichiro,Takeda Masayuki,Masuyama Keisuke,Araki Isao,Yamada Shizuo
Journal of Pharmacological Sciences, 2014
… The Ki for imidafenacin in the human bladder approximately corresponded to pharmacological potency for the competitive blockade of carbachol-induced contractions of bladder, indicating a close correlation between binding affinity of imidafenacin to bladder muscarinic receptors and its pharmacological effects in the bladder. …
NAID 130003382631

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★リンクテーブル★

リンク元	「カルバコール」「carbamylcholine」

「カルバコール」

Carbachol
Systematic (IUPAC) name
	2-[(Aminocarbonyl)oxy]-N,N,N-trimethylethanaminium chloride
Clinical data
Trade names	Miostat
AHFS/Drugs.com	Monograph
Pregnancy; category	US: C (Risk not ruled out); ;
Routes of; administration	Oral-Tablet, Injectable-solution, Topical-eye drops
Legal status
Legal status	℞ (Prescription only);
Pharmacokinetic data
Bioavailability	low
Metabolism	?
Biological half-life	?
Excretion	?
Identifiers
CAS Number	51-83-2
ATC code	N07AB01 (WHO) S01EB02 (WHO) QA03AB92 (WHO)
PubChem	CID 5831
IUPHAR/BPS	298
DrugBank	DB00411
ChemSpider	5626
UNII	8Y164V895Y
KEGG	D00524
ChEBI	CHEBI:3385
ChEMBL	CHEMBL14
Chemical data
Formula	C6H15ClN2O2
Molar mass	182.696 g/mol
	SMILES [Cl-].O=C(OCC[N+](C)(C)C)N ;
	InChI InChI=1S/C6H14N2O2.ClH/c1-8(2,3)4-5-10-6(7)9;/h4-5H2,1-3H3,(H-,7,9);1H ; Key:AIXAANGOTKPUOY-UHFFFAOYSA-N ;
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