Carbachol

Carbachol
Names
Trade namesMiostat, others
Other namesCarbamylcholine
IUPAC name
  • 2-[(Aminocarbonyl)oxy]-N,N,N-trimethylethanaminium chloride
Clinical data
Drug classCholinergic agonist[1]
Main usesGlaucoma, eye surgery[1]
Side effectsEye discomfort, headache, blurry vision, trouble seeing in low light, red eyes[1]
Pregnancy
category
  • AU: B2
  • US: C (Risk not ruled out)
    Routes of
    use    		By mouth (tablets)
    Solution for injection
    Eye drop
    External links
    AHFS/Drugs.comMonograph
    Legal
    License data
    Legal status
    • In general: ℞ (Prescription only)
    Pharmacokinetics
    BioavailabilityLow
    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 checkY
    • Key:AIXAANGOTKPUOY-UHFFFAOYSA-N checkY

    Carbachol, sold under the brand name Miostat among others, is a medication used to treat glaucoma or during eye surgery.[1] Usually other agents such as pilocarpine or acetylcholine preferred.[1] It is used as an eye drop or injected into the eye.[1]

    Common side effects include eye discomfort, headache, blurry vision, trouble seeing in low light, and red eyes.[1] Other side effects may include allergic reactions, retinal detachment, diarrhea, low blood pressure, sweating, and arrhythmias.[1] Safety in pregnancy is unclear.[1] It is a cholinergic agonist that binds and activates acetylcholine receptors.[1]

    Carbachol was approved for medical use in the United States in 1972.[1] It is on the World Health Organization's List of Essential Medicines as an alternative to pilocarpine.[2] In the United States the solution for injection into the eye costs about 27 USD per dose as of 2021.[3]

    Medical uses

    Carbachol is primarily used in the treatment of glaucoma, but it is also used during ophthalmic surgery.[4] 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.[4][5]

    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).[6]

    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 therefore 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.[7]

    Pharmacology

    Carbachol is a choline carbamate and a positively charged quaternary ammonium compound.[4] 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.[4] 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.[4]

    Carbachol is a parasympathomimetic that stimulates both muscarinic and nicotinic receptors.[4] In topical ocular and intraocular administration its principal effects are miosis and increased aqueous humour outflow.[4]

    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).[4]

    A recent review indicates that carbachol is a strong promoter of ICC activity, which is mediated through the calcium-activated chloride channel, anoctamin 1.[8]

    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.

    References

    1. 1 2 3 4 5 6 7 8 9 10 11 "Carbachol Monograph for Professionals". Drugs.com. Archived from the original on 29 April 2021. Retrieved 29 December 2021.
    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. ↑ "Miostat Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 17 January 2021. Retrieved 29 December 2021.
    4. 1 2 3 4 5 6 7 8 "Carbachol". PubChem Compound. Archived from the original on 6 March 2014. Retrieved 6 March 2014.
    5. ↑ "Carbachol generics". ndrugs. Archived from the original on 30 January 2016. Retrieved 6 March 2014.
    6. ↑ Harvey RA, Champe PC, eds. (2009). Lippincott's Illustrated Review: Pharmacology (4th ed.). Lippincott Williams & Wilkins. p. 49. ISBN 978-0-7817-7155-9.
    7. ↑ "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)
    8. ↑ 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.
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