07.02.3 Muscarinic Agonists

The most logical way to mimic the parasympathetic nervous system is to give acetylcholine. Acetylcholine is not active after oral administration, and intravenous acetylcholine has widespread peripheral effects, some of which are beneficial and some of which are detrimental. As a quaternary ammonium compound, acetylcholine does not penetrate the central nervous system after intravenous administration, and consequently has no central effects. Acetylcholine is rapidly degraded by the enzyme pseudocholinesterase, and is found in the plasma, which means that acetylcholine has a very short half-life. For all these reasons, acetylcholine is not suitable for clinical use.

Pilocarpine is a muscarinic agonist that can by used clinically. Pilocarpine is a naturally occurring cholinomimetic alkaloid, which does not have much similarity to acetylcholine in structure, but does selectively stimulate muscarinic receptors. Pilocarpine is used topically. Pilocarpine is resistant to cholinesterases, which means they have a longer action than acetylcholine. Pilocarpine is selective for muscarinic receptors, and is used to mimic particular effects of the parasympathetic nervous system.

On the eye, acetylcholine stimulates aqueous humour outflow, and when the aqueous humour leaves the eye, the intraocular pressure decreases. Pilocarpine eye drops are used in glaucoma to increase aqueous humour outflow, which decreases intraocular pressure and the damage caused by an increased intraocular pressure. The miotic action of stimulating muscarinic receptors with pilocarpine also reverses the sight distortions associated with glaucoma.