Althoughβagonists also mediate metabolic effects, such as the conversion of glycogen
to glucose (glycogenolysis) in both liver and skeletal muscle, these effects have not yet
been amenable to meaningful therapeutic exploitation.
4.3.6.4 β-Adrenergic Antagonists
β antagonists (or β-blockers) are perhaps the most important adrenergic drugs
since they are used not only for neurological indications but also for a wide variety of
non-neurologic indications in organ systems throughout the body, reflecting the
far-reaching and pervasive influence of adrenergic neurotransmitter messenger mole-
cules. Beta-blockers have been used extensively in the management of systemic arter-
ial hypertension, a disease very prevalent in the Western world. Arterial hypertension
(“high blood pressure”), sometimes called “the silent killer,” predisposes to stroke,
heart attack, and peripheral vascular disease. Hypertension may be either systolic (pres-
sure against arterial wall during heart contraction) or diastolic (pressure against arterial
wall at rest) as defined by the blood pressure recording (systolic/diastolic). If the pres-
sure is high for prolonged periods of time, it leads to damage of the arterial wall, which
in turn predisposes to atherosclerosis with thickening of the arterial wall and narrowing
of the arterial diameter. Hypertension may be treated with a number of agents, including
β-blockers, diuretics, and angiotensin converting enzyme (ACE) inhibitors.
In addition, β-blockers may be used for other cardiovascular indications. For
instance,βantagonists protect the heart by blocking cardiac workload above basal
levels; this effect is used prophylactically in the treatment of angina pectoris (a tight,
squeezing retrosternal chest pain arising from decreased blood supply to the muscles
of the heart as a result of partial blockage of a coronary artery). Beta-blockers also
slow the heart rate, and thus may be employed to treat tachyarrhythmias (also called
tachycardia)—a disorder characterized by too high a heart rate. As a side effect,
β-blockers can cause bradycardia (too slow a heart rate), and can worsen an underlying
asthmatic propensity.
Certainβ-blockers are also used to treat neurologic disorders, such as migraine
headache and benign essential tremor. Tremor may be defined as a more or less regu-
lar, rhythmic oscillation of a body part around a fixed point, usually in one plane.
Benign essential tremor is a common familial disorder affecting 415 out of 100,000
adults over the age of 40 years. The tremor has a frequency of 6–8 Hz and may affect
the head, larynx (and thus voice), or upper extremities. Beta-blockers may also be
exploited for their anxiolytic actions whereby they reduce hand trembling and chest
palpitations in people undergoing emotional stress. Musicians competing in classical
music competitions, public orators, and even championship snooker players have
all been known to take β-blockers to settle the “shakes” prior to major competitions—
representing another aspect of “drug doping” in competitive sports. Finally, when
applied topically to the eye,β-blockers can be used to treat glaucoma (increased pres-
sure within the orb of the eye).
Structurally,β antagonists are much closer to βagonists than to either their αcoun-
terparts or anticholinergic agents. The first useful βantagonist, discovered in 1948, was
dichloroisoproterenol (4.62, DCI), obtained by simple replacement of the catechol
234 MEDICINAL CHEMISTRY