4.2 ACETYLCHOLINE AND THE CHOLINERGIC RECEPTORS
From the perspective of drug design, acetylcholine is one of the most important neuro-
transmitters in the human brain; neurons that use acetylcholine as a neurotransmitter are
referred to as cholinergicneurons. The cholinergic neuronal system can be found in the
CNS (especially in the cortex and caudate nucleus), in the autonomic nervous system,
and in the sensorimotor system. Acetylcholine (ACh) is the neurotransmitter in all gan-
glia, the neuromuscular junction, and the postganglionic synapses of the parasympa-
thetic nervous system. However, the autonomic innervation of most organs utilizes both
the parasympathetic (mediated by cholinergic neurotransmitters) and sympathetic
(mediated by adrenergic neurotransmitters, section 4.3) systems, with the effects of the
two usually being opposed. Table 4.1 shows the varying effects of cholinergic and
adrenergic stimulation on a diversity of organ systems throughout the body. Thus, if one
system causes an increase in some physiological action, the other will cause a decrease,
and vice versa.204 MEDICINAL CHEMISTRY
Table 4.1Responses of Effector Organs to Autonomic Nerve Impulses and Circulating
Catecholamines
Cholinergic impulses Adrenergic impulses
Response Receptor Response
Effector organs type
Heart
S-A node Decrease in heart rate; β Increase in heart rate
Vagal arrest
Atria Decrease in contractility β Increase in contractility and
and (usually) increase in conduction velocity
conduction velocity
A-V node and Decrease in conduction β Increase in conduction velocity
conduction system velocity; A-V block
Ventricles – β Increase in contractility,
conduction velocity,
automaticity, and rate
of idiopathic pacemakers
Blood vessels
Coronary Dilatation α Constriction
β Dilatation
Skin and mucosa – α Constriction (slight)
Skeletal muscle Dilatation α Constriction
β Dilatation
Cerebral – α Constriction (slight)
Pulmonary – α Constriction
Abdominal viscera – α Constriction
β Dilatation
Renal – α Constriction
(Continued)