Carbachol
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| Clinical data | |
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| Trade names | Miostat |
| AHFS/Drugs.com | Monograph |
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| Routes of administration | By mouth(tablets) Solution for injection Topical(ophthalmic solution) |
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| Pharmacokineticdata | |
| Bioavailability | Low |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.000.117 |
| Chemical and physical data | |
| Formula | C6H15ClN2O2 |
| Molar mass | 182.65g·mol−1 |
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Carbachol,also known ascarbamylcholineand sold under the brand nameMiostatamong others, is acholinomimeticdrugthat binds and activatesacetylcholine receptors.Thus it is classified as acholinergic agonist.It is primarily used for variousophthalmicpurposes, such as for treatingglaucoma,or for use during ophthalmic surgery. It is generally administered as an ophthalmic solution (i.e.,eye drops).
Carbachol produces effects comparable to those ofsarinif a massive overdose is administered (as may occur following industrial and shipping accidents) and therefore it is classified as anextremely hazardous substancein 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]
It is on theWorld Health Organization's List of Essential Medicines.[2]
Chemistry and pharmacology
[edit]Carbachol is acholinecarbamateand a positively charged quaternary ammonium compound.[3]It is not well absorbed in thegastro-intestinal tractand does not cross theblood–brain barrier.It is usually administered topical ocular or through intraocular injection.[3]Carbachol is not easily metabolized bycholinesterase,it has a 2 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 chlorideis mixed in to promote absorption.[3]
Carbachol is aparasympathomimeticthatstimulatesbothmuscarinicandnicotinicreceptors.[3]In topical ocular and intraocular administration its principal effects aremiosisand increasedaqueous humouroutflow.[3]
In thecatandrat,carbachol is well known for its ability to inducerapid eye movement(REM) sleep when microinjected into thepontine reticularformation. Carbachol elicits this REM sleep-like state via activation of postsynaptic muscariniccholinergicreceptors (mAChRs).[3]
A recent review indicates that carbachol is a strong promoter ofICCactivity, which is mediated through thecalcium-activated chloride channel,anoctamin 1.[4]
Synthesis
[edit]Carbachol may be prepared in a 2 step process beginning with the reaction of2-chloroethanolwithureato form a 2-chloroethyl-carbamate,which is thenquaternisedby a reaction withtrimethylamine.
Indications
[edit]Carbachol is primarily used in the treatment ofglaucoma,but it is also used during ophthalmic surgery.[3]Carbachol eyedrops are used to decrease the pressure in the eye for people with glaucoma. It is sometimes used to constrict the pupils duringcataractsurgery.
Topical ocular administration is used to decrease intraocular pressure in people with primary open-angleglaucoma.Intraocular administration is used to produce miosis after lens implantation during cataract surgery. Carbachol can also be used to stimulate bladder emptying to treat the condition of underactive bladder.[5]
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.[3][6]
Contraindications
[edit]Use of carbachol, as well as all othermuscarinic receptor agonists,is contraindicated in patients withasthma,coronary insufficiency,gastroduodenalulcers,andincontinence.[citation needed]Theparasympathomimeticaction of this drug will exacerbate thesymptomsof these disorders.[citation needed]
Overdose
[edit]The effects of a systemic overdose will probably be similar to the effects of anerve 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).[7]
References
[edit]- ^"40 C.F.R.: Appendix A to Part 355—The List of Extremely Hazardous Substances and Their Threshold Planning Quantities"(PDF)(1 July 2008 ed.).Government Printing Office.Archived fromthe original(PDF)on 25 February 2012.Retrieved29 October2011.
- ^World Health Organization(2021).World Health Organization model list of essential medicines: 22nd list (2021).Geneva: World Health Organization.hdl:10665/345533.WHO/MHP/HPS/EML/2021.02.
- ^abcdefgh"Carbachol".PubChem Compound.Retrieved6 March2014.
- ^Sanders KM, Zhu MH, Britton F, Koh SD, Ward SM (February 2012)."Anoctamins and gastrointestinal smooth muscle excitability".Experimental Physiology.97(2): 200–206.doi:10.1113/expphysiol.2011.058248.PMC3272164.PMID22002868.
- ^Moro C, Phelps C, Veer V, Clark J, Glasziou P, Tikkinen KA, Scott AM (January 2022)."The effectiveness of parasympathomimetics for treating underactive bladder: A systematic review and meta-analysis"(PDF).Neurourology and Urodynamics.41(1): 127–139.doi:10.1002/nau.24839.PMID34816481.S2CID244530010.
- ^"Carbachol generics".ndrugs.Retrieved6 March2014.
- ^Harvey RA, Champe PC, eds. (2009).Lippincott's Illustrated Review: Pharmacology(4th ed.). Lippincott Williams & Wilkins. p. 49.ISBN978-0-7817-7155-9.
External links
[edit]- "Carbachol".Drug Information Portal.U.S. National Library of Medicine.
