MUSCARINIC AGONISTS

Muscarinic agonists are used in ophthalmology in the treatment of glaucoma. The alkaloid atropine 3.20 was obtained from the plant, deadly nightshade, Atropa belladonna, which was used in the Middle Ages both because of its properties in dilating the pupils of the eye supposedly to make women more glamorous and also because of its poisonous effects. Atropine is a muscarinic antagonist. It binds competitively and prevents acetylcholine from functioning. It dilates the pupil of the eye and hence it is used in ophthalmology. Atropine is relatively lipophilic and as the free amine, it can cross the blood:brain barrier and produce effects on the CNS. However, quaternary salts of atropine such as ipratropium bromide 3.21 do not cross the blood:brain barrier and are used as muscarinic antagonists in bronchial dilation and muscle relaxation.

Cholinergic agonists have some other medicinal applications. Bethanechol 3.22 is a carbamate rather than an ester and therefore it is not easily hydrolysed by acetylcholine esterase increasing its persistence. It stimulates muscarinic receptors and it is used to facilitate urinary expulsion. The alkaloid pilocarpine 3.23 is a g-lactone and is also stable to acetylcholinesterase. It exhibits muscarinic activity and it is used in ophthalmology to stimulate secretion from the eye and hence reduce intraocular pressure in glaucoma. It is helpful to see a similarity in this structure both to acetylcholine and to muscarine.