Chemistry:Carbachol

Short description: Chemical compound

Carbachol

Clinical data
Trade names	Miostat
AHFS/Drugs.com	Monograph
License data	US DailyMed: Carbachol
Pregnancy category	AU: B2 US: C (Risk not ruled out)
Routes of administration	By mouth (tablets) Solution for injection Topical (ophthalmic solution)
ATC code	N07AB01 (WHO) S01EB02 (WHO) QA03AB92 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	Low
Identifiers
IUPAC name 2-[(Aminocarbonyl)oxy]-N,N,N-trimethylethanaminium chloride
CAS Number	51-83-2 Y
PubChem CID	5831
IUPHAR/BPS	298
DrugBank	DB00411 Y
ChemSpider	5626 Y
UNII	8Y164V895Y
KEGG	D00524 Y
ChEBI	CHEBI:3385 Y
ChEMBL	ChEMBL14 Y
PDB ligand	CCE (PDBe, RCSB PDB)
Chemical and physical data
Formula	C6H15ClN2O2
Molar mass	182.65 g·mol−1
3D model (JSmol)	Interactive image
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
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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 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.

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

Chemistry and pharmacology

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

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

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).

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

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. 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.

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.

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).

External links

• "Carbachol". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/name/carbachol.