Some of the many pharmacological derivatives of epinephrine and norepinephrine are shown in Figure 1 with an indication of the adrenergic receptors with which they interact (also see Figure 2). A brief description of these examples will serve to indicate the wide-ranging uses of the drugs belonging to this group. Phenylephrine is currently the most commonly marketed decongestant in over-the-counter cold and cough medications. It is not as effective as pseudoephedrine, which has become subject to controls to prevent its use in the production of methamphetamines. Ephedrine and pseudoephedrine, both found in the Chinese herb members of the Ephedra family, ma huang, act indirectly to increase the biological activity of endogenous catacholamines. Isoproterenol is used to treat bradycardia (a resting heartbeat of less than 50 beats per minute in a clinical context). In the past it has also been used as a bronchodilator but albuterol, with greater receptor specificity, has largely replaced isoproterenol for this use.
Fig1. Some catecholamine pharmacological agents. Three classes of drugs relating to epinephrine and norepinephrine are shown: A. Epinephrine agonists; B. antagonists interacting with β-adrenergic receptors; C. Antagonists of α-adrenergic receptors. The receptor type(s) with which the molecule interacts most effectively is shown in parenthesis. See Figure 2 for the classification of the adrenergic receptors.
Fig2. Adrenergic receptors. The adrenergic receptors, which bind epinephrine and norepinephrine (as well as synthetic compounds such as those in Figure 1) are classified into three major groups, α1, α2, and β, based on pharmacological properties and type of signaling system. The features of these three groups are shown in this figure. The subtypes within each group are listed below the major example shown. All of the adrenergic receptors are G-protein coupled receptors (GPCRs) containing seven membrane-spanning regions. In the structural depictions of the receptors at the top, the approximate locations of extracellular N-glycosylation sites are shown (Y), as are the intracellular loop (green) and the carboxy terminal tail (magenta). The signaling systems are shown at the bottom of the figure, where the major Gα protein to which the receptor is coupled is indicated (tan circle) along with the primary enzymatic activity affected (PLC, phospholipase C; AC-adenyl cyclase) and the effect on the second messenger (increased ionized calcium, decreased or increased cyclic AMP).
Propanolol is a blocker of β-adrenergic receptors and is widely used to counter hypertension and anxiety. Atenolol is a more cardio-specific drug used for acute myocardial infarction and tachycardia (more than 100 beats per minute at rest) due, for example, to hyperthyroidism. Timbol is most often found in opthalmic solutions to treat glaucoma. Phentolamine is used to reverse dental anesthesia and phenoxybenzamine is an antihypertensive agent, particularly used in the treatment of pheochromocytoma.
