Receptors of the sympathetic system may be divided into alpha
(α), beta (β), and dopamine (D)
receptors. Drugs that bind to these receptors and modulate or mimic
the function of the sympathetic nervous system may be divided into
those which augment the system (sympathomimetics)
and those which antagonize the system (sympatholytics).
The sympathomimetics constitute a very important group of agonists
used for cardiovascular, respiratory, and other conditions. They
are readily divided into subgroups on the basis of their spectrum
of affinity for α, β, or D receptors.
Alternatively, sympathomimetics may be divided into subgroups based
on whether their mode of action is direct or indirect. Sympatholytics
are an important group of antagonists used in cardiovascular and
other conditions. These drugs are divided into primary subgroups
on the basis of their receptor (α and β)
Sympathomimetics (also called adrenomimetics)
may directly activate their adrenoceptors, or they may act indirectly
to increase the concentration of catecholamine transmitter in the
synapse (Figure 6–1). Amphetamine derivatives and tyramine
cause the release of stored catecholamines; these sympathomimetics
are, therefore, mainly indirect in their mode of action. Another
form of indirect action is seen with cocaine and the tricyclic antidepressants;
these drugs inhibit reuptake of catecholamines by presynaptic nerve terminals
that release them (Figure 4–3), and thus increase the synaptic
activity of released transmitter.
Sympathomimeticdrugs are readily divided into subgroups
on the basis of which receptors they activate: alpha, beta, or dopamine
(not shown). Alternatively, these drugs are divided into subgroups
on the basis of whether their mode of action is direct (at postsynaptic
receptors) or indirect (other than at postsynaptic receptors).
Blockade of metabolism (i.e., block of catechol-O-methyltransferase [COMT] and monoamine
oxidase [MAO]) has little direct effect on autonomic activity,
but MAO inhibition increases the stores of catecholamines in adrenergic
synaptic vesicles and thus may potentiate the action of other indirect-acting
sympathomimetics subsequently discussed.
Both α and β receptors are
further subdivided into subgroups. The distribution of these receptors
is set forth in Table 4–3. Epinephrine may be considered
a single prototype with effects at all receptor types (α1, α2, β1, β2,
and β3). In addition, separate prototypes—phenylephrine for α receptors
and isoproterenol for β receptors—have
been characterized. Dopamine receptors constitute a third class
of adrenoceptors. The just-mentioned drugs have relatively little
effect on dopamine receptors, but dopamine itself is a potent dopamine
receptor agonist and when given as a drug can also activate β receptors
(intermediate doses) and α receptors (large doses).
The relative affinities of these representative drugs are presented
in Table 6–1.
Table 6–1. Relative
Selectivity of ...