Carbachol

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).

References

References

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2. (2021). "World Health Organization model list of essential medicines: 22nd list (2021)". World Health Organization.
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4. (February 2012). "Anoctamins and gastrointestinal smooth muscle excitability". Experimental Physiology.
5. (January 2022). "The effectiveness of parasympathomimetics for treating underactive bladder: A systematic review and meta-analysis". Neurourology and Urodynamics.
6. "Carbachol generics". ndrugs.