The sympathomimetics constitute a very important group of drugs used for cardiovascular, respiratory, and other conditions. They are readily divided into subgroups on the basis of their spectrum of action (α-, β-, or dopamine-receptor affinity) or mode of action (direct or indirect).
Adrenoceptors are classified as α, β, or dopamine receptors; these groups are further subdivided into subgroups. The distribution of these receptors is set forth in Table 9–1. Epinephrine may be considered a single prototype agonist with effects at all α- and β-receptor types. Alternatively, separate prototypes, phenylephrine (an α agonist) and isoproterenol (β), may be defined. 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 (larger doses).
TABLE 9–1Types of adrenoceptors outside the CNS, some of the peripheral tissues in which they are found, and their major effects. ||Download (.pdf) TABLE 9–1 Types of adrenoceptors outside the CNS, some of the peripheral tissues in which they are found, and their major effects.
|Type ||Tissue ||Actions |
|Alpha1 (α1) ||Most vascular smooth muscle ||Contracts (↑ vascular resistance) |
| ||Pupillary dilator muscle ||Contracts (mydriasis) |
| ||Pilomotor smooth muscle ||Contracts (erects hair) |
| ||Bladder trigone, prostatic smooth muscle ||Contraction |
| ||Liver (in some species, eg, rat) ||Stimulates glycogenolysis |
|Alpha2 (α2) ||Adrenergic and cholinergic nerve terminals ||Inhibits transmitter release |
| ||Platelets ||Stimulates aggregation |
| ||Some vascular smooth muscle ||Contracts |
| ||Adipocytes ||Inhibits lipolysis |
| ||Pancreatic β (B) cells ||Inhibits insulin release |
|Beta1 (β1) ||Heart ||Stimulates rate and force |
| ||Juxtaglomerular cells of kidney ||Stimulates renin release |
|Beta2 (β2) ||Airways, uterine, and vascular smooth muscle ||Relaxes |
| ||Liver (human) ||Stimulates glycogenolysis |
| ||Pancreatic β (B) cells ||Stimulates insulin release |
| ||Somatic motor neuron terminals (voluntary muscle) ||Causes tremor |
| ||Heart ||Stimulates rate and force |
|Beta3 (β3) ||Adipocytes ||Stimulates lipolysis |
|Dopamine1 (D1) ||Renal and other splanchnic blood vessels ||Dilates (↓ resistance) |
|Dopamine2 (D2) ||Nerve terminals ||Inhibits adenylyl cyclase |
Sympathomimetic agonists may directly activate their adrenoceptors, or they may act indirectly to increase the concentration of endogenous catecholamine transmitter in the synapse. Amphetamine derivatives and tyramine cause the release of stored catecholamines; they are therefore mainly indirect in their mode of action. Cocaine and certain antidepressants exhibit another form of indirect action; these drugs inhibit reuptake of catecholamines by the norepinephrine transporter (NET) and the dopamine transporter (DAT) in nerve terminals (see Figure 6–2) and thus increase the synaptic activity of released transmitter. The complex actions of antidepressants on amine reuptake are discussed in Chapter 30.