Carbachol

Carbachol, also known as carbamylcholine and sold under the brand name Miostat among others, is a cholinomimetic drug that binds and activates acetylcholine receptors. 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., eye drops).

Carbachol
Clinical data
Trade namesMiostat
AHFS/Drugs.comMonograph
License data
Pregnancy
category
  • AU: B2
Routes of
administration		By mouth (tablets)
Solution for injection
Topical (ophthalmic solution)
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
BioavailabilityLow
Identifiers
IUPAC name
  • 2-[(Aminocarbonyl)oxy]-N,N,N-trimethylethanaminium chloride
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.000.117
Chemical and physical data
FormulaC6H15ClN2O2
Molar mass182.65 g·mol−1
3D model (JSmol)
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 Y
  • Key:AIXAANGOTKPUOY-UHFFFAOYSA-N Y
  (verify)

Carbachol produces effects comparable to those of sarin if a massive overdose is administered (as may occur following industrial and shipping accidents) and therefore 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]

It is on the World Health Organization's List of Essential Medicines.[2]

Chemistry and pharmacology

Carbachol is a choline carbamate and a positively charged quaternary ammonium compound.[3] 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.[3] Carbachol is not easily metabolized by cholinesterase, 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 chloride is mixed in to promote absorption.[3]

Carbachol is a parasympathomimetic that stimulates both muscarinic and nicotinic receptors.[3] In topical ocular and intraocular administration its principal effects are miosis and increased aqueous humour outflow.[3]

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).[3]

A recent review indicates that carbachol is a strong promoter of ICC activity, which is mediated through the calcium-activated chloride channel, anoctamin 1.[4]

Synthesis

Carbachol may be prepared in a 2 step process beginning with the reaction of 2-chloroethanol with urea to form a 2-chloroethyl-carbamate, which is then quaternised by a reaction with trimethylamine.

Indications

Carbachol is primarily used in the treatment of glaucoma, 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 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 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

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).[7]

References
  1. "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 from the original (PDF) on 25 February 2012. Retrieved 29 October 2011. {{cite journal}}: Cite journal requires |journal= (help)
  2. 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.
  3. "Carbachol". PubChem Compound. Retrieved 6 March 2014.
  4. 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.
  5. Moro, Christian; Phelps, Charlotte; Veer, Vineesha; Clark, Justin; Glasziou, Paul; Tikkinen, Kari A. O.; Scott, Anna M. (24 November 2021). "The effectiveness of parasympathomimetics for treating underactive bladder: A systematic review and meta-analysis". Neurourology and Urodynamics. 41 (1): 127–139. doi:10.1002/nau.24839. ISSN 1520-6777. PMID 34816481. S2CID 244530010.
  6. "Carbachol generics". ndrugs. Retrieved 6 March 2014.
  7. Harvey RA, Champe PC, eds. (2009). Lippincott's Illustrated Review: Pharmacology (4th ed.). Lippincott Williams & Wilkins. p. 49. ISBN 978-0-7817-7155-9.
  • "Carbachol". Drug Information Portal. U.S. National Library of Medicine.
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