- Modification of the intermediate aminoethanol side chainbetween the catechol and
the terminal amine can produce surprising effects, as exemplified by prenalterol
(4.59), in which the insertion of an oxygen and a carbon atom between the alcohol
and phenyl groups changes the parent compound (β 2 /β 1 =11.5) into a very selective
β 1 agonist (β 2 /β 1 =0.075). Although many of these βagonists are useful in the
management of heart failure, their apparently “cardioselective” (β 1 ) activity does not
necessarily reflect true receptor selectivity. - Tertiary amines are not active; the β 2 activity of secondary amines is increased by
branched arylalkyl chains.
These basic design principles have been of value in the design and synthesis of varying
β agonists with varying βreceptor selectivities.
Althoughβagonists (as well as βantagonists) have been thoroughly investigated for
many years, active compounds have continued to emerge over the past decade, reflect-
ing the immense clinical importance of these classes of drugs. βagonists have many
potential therapeutic benefits. By stimulating β 1 receptors, hence activation of adenylate
cyclase and cAMP,β 1 agonists augment all heart functions including force of contrac-
tion (systolic force, inotropism), rate of contraction (sinoatrial rate, chronotropism), and
electrical conduction velocity within the heart (conduction velocity, dromotropism).
Although, in theory,β 1 agonists would be valuable in heart failure, their use does carry
the risk of cardiac arrhythmias. Nevertheless, the cardiostimulatory effects of βagonists
such as epinephrine is exploited in the treatment of cardiac arrest. β 2 agonists produce a
uterine relaxant effect and may be used in obstetrics to prevent premature labour.
However,β 2 agonists enjoy a much wider application in the treatment of lung disease.
Treatment of Asthma. Broadly speaking, pulmonary diseases can be categorized into
two broad groups:restrictive lung diseases(in which lung compliance is reduced,
resulting in inadequate pulmonary inflation) and obstructive lung diseases (in which
the tubes transporting air to and from the lungs [bronchi, bronchioles] are reduced in
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