Cholinomimetic Receptor Agonists

Methacholine, carbachol, and bethanechol are all agents that mimic the effects of stimulation of cholinergic nerves. 

The miotic effects of carbachol and bethanechol are greater than those of acetylcholine. Atropine is able to antagonize all cholinergic (muscarinic) effects produced by acetylcholine, methacholine, carbachol, and bethanechol. However, this antagonism is least evident with carbachol. 

Bethanechol is of value in the management of postoperative abdominal distention, gastric atony or stasis, and urinary retention. Carbachol (0.25 to 3.00%) may be used for the long-term therapy of noncongestive wide-angle glaucoma. 

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Pilocarpine is a naturally occurring cholinomimetic alkaloid that is structurally distinct from the choline esters. It is a tertiary amine that crosses membranes relatively easily. Therefore, it is rapidly absorbed by the cornea of the eye, and it can cross the blood-brain barrier. Pilocarpine is a pure muscarinic receptor agonist, and it is unaffected by cholinesterases. Muscarine is an alkaloid with no therapeutic use, but it can produce dangerous cholinomimetic stimulation following ingestion of some types of mushrooms (e.g., Inocybes). 

Classical studies by Sir Henry Dale demonstrated that the receptors activated by muscarine, an alkaloid isolated from the mushroom Amanita muscaria, are the same receptors activated by ACh released from parasympathetic nerve endings, from which the general notion that muscarinic agonists have parasympathomimetic properties was born. This conclusion is true but incomplete, and we now know that muscarinic receptors have a broader distribution and many functional roles. To understand the actions of cholinomimetic drugs it is essential to recognize that muscarinic receptors (1) mediate the activation of effectors by ACh released from parasympathetic nerve... 

An alkaloid of natural plant origin, pilocarpine is a direct-acting cholinergic agonist with a dominant action at both peripheral and central muscarinic sites. The cholinomimetic action of pilocarpine on smooth muscle muscarinic receptors generally results in contraction.The response of intraocular smooth muscle to pilocarpine is pupillary constriction, spasm of accommodation, and reduction of lOP. 

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