When synaptic transmission depends upon acetylcholine as the
primary neurotransmitter, it is labeled cholinergic.
The termination of acetylcholine activity is mediated by the enzymeacetylcholinesterase. There are two subtypes of cholinergic receptors,
muscarinic (M) and nicotinic (N). Agonists that mimic the effects
of acetylcholine are defined as cholinomimetics. Some drugs are direct-acting agonists for the cholinergic receptors
(Figure 5–1). Other drugs function as indirect-acting agonists
by preventing the inactivation of acetylcholine. Antagonists that
inhibit acetylcholine at muscarinic or nicotinic receptors are defined
as anticholinergics. Drugs that selectively
inhibit muscarinic receptors are called antimuscarinics (Figure
5–2), whereas those that selectively inhibit nicotinic
receptors are antinicotinics.
Algorithm of cholinomimetic drugs. Some drugs are direct-acting
agonists that stimulate the muscarinic or nicotinic receptors. Alternatively,
the drugs may be indirect-acting in that they inhibit the enzymeacetylcholinesterase that is responsible for terminating the action
Grouping of cholinoreceptor direct-acting antagonists
based on their inhibition of either muscarinic (M) or nicotinic
(N) receptors. Further subdivisions for the muscarinic receptors
include drugs that are specific antagonists of M1 receptors
located on nerve endings or nonspecific muscarinic antagonists.
Nicotinic antagonists are subdivided based on whether the drug inhibits
postsynaptic receptors at the neuromuscular junction (NM)
or postsynaptic receptors in the parasympathetic and sympathetic
The subtypes of cholinoreceptors are set forth in Table 5–1.
At present, subtype-selective agonists for the muscarinic receptors
are not clinically available. Direct-acting nicotinic agonists may
be classified on the basis of whether ganglionic (NN) or
neuromuscular (NM) stimulation predominates, but agonist
selectivity is very limited. Several molecular mechanisms for receptor
signaling have been identified for muscarinic receptors (Table 5–1).
In general, these receptors modulate the formation of second messengers
or the activity of ion channels. In contrast, all nicotinic receptors
cause the opening of a channel selective for sodium and potassium that
results in cellular depolarization. This signaling mechanism occurs
in the autonomic ganglia and at the neuromuscular junction.
Table 5–1. Subtypes
and Characteristics of Cholinoceptors ||Download (.pdf)
Table 5–1. Subtypes
and Characteristics of Cholinoceptors
|Receptor Type||Location||Postreceptor Mechanism1|
|M1||Nerves||IP3, DAG cascade|
|M2||Heart, nerves, smooth muscle||Inhibition of cAMP production, activation of K+ channels|
|M3||Glands, smooth muscle, endothelium||IP3, DAG cascade|
|M42||CNS3||Inhibition of cAMP production|
|M52||CNS3||IP3, DAG cascade|
|NM||Skeletal muscle neuromuscular junction||Na+, K+ depolarizing
|NN||Postganglionic cell body, dendrites||Na+, K+ depolarizing