5.10: Direct-Acting Cholinergic Agonists: Therapeutic Uses

Direct-acting cholinergic agonists have many therapeutic uses in various medical fields. Choline esters, including acetylcholine, have limited clinical utility due to their non-selectivity and short duration of action. Still, acetylcholine and carbachol are applied topically during ophthalmologic surgery to induce miosis. Pilocarpine, a muscarinic and ganglionic stimulator, effectively treats open-angle glaucoma and alleviates xerostomia and dry mouth caused by radiotherapy or Sjögren syndrome. Cevimeline, a selective M₃ agonist, is preferred over pilocarpine as a sialogogue because of fewer side effects. Bethanechol is used for postoperative or postpartum urinary retention, neurogenic bladder issues, congenital megacolon, and gastroesophageal reflux symptoms. Methacholine is administered via inhalation to identify bronchial airway hyperreactivity in nonasthmatic patients.

Cholinomimetic alkaloids, such as arecoline, exhibit muscarinic and nicotinic actions on skeletal muscle and platelets. Despite its central nervous system effects, arecoline neither enhances cognitive functions nor offers therapeutic benefits. In conclusion, direct-acting cholinergic agonists are crucial in treating specific medical conditions. Still, their beneficial use is decided based on a judgment that weighs their selectivity and potential side effects.

Direct-acting cholinergic agonists comprise choline esters such as acetylcholine, methacholine and bethanechol and alkaloids such as pilocarpine and cevimeline. They have diverse therapeutic applications.

During eye surgery, acetylcholine is used to constrict the pupils. However, its application is limited by its non-selectivity and temporary effects.

Methacholine stimulates muscarinic receptors in the airways. Its inhalation is used to diagnose bronchial airway hyperreactivity. The degree of airway narrowing helps diagnose asthma and its severity.

Another muscarinic stimulator, bethanechol, improves gastrointestinal and urinary tract contractions, relieving constipation and the inability to urinate. 

Eye drops containing pilocarpine, a muscarinic and ganglionic stimulator,  are used to lower intraocular pressure and treat glaucoma.

Cevimeline is a selective M₃ agonist. It is used to help patients with dry mouth or eyes by increasing salivation and lacrimal secretion.