diameter, hindering air entry and promoting air trapping within the lungs); of these two
groups, obstructive diseases are much more common.The restrictive diseases are usu-
ally caused by infiltrative diseases of the lung, such as silicosis, farmer’s lung or coal
miner’s pneumoconiosis. The obstructive diseases may be either acute (e.g.,asthma) or
chronic (e.g.,emphysema, chronic bronchitis; collectively these latter two disorders are
called chronic obstructive pulmonary disease [COPD]). Asthma is the prototypic
obstructive lung disease and is a medical disorder in which therapeutic manipulation of
adrenergic messengers has been of crucial importance; accordingly,β 2 agonists play a
central role in the day-to-day management of obstructive pulmonary diseases.
Asthma is characterized by recurrent episodic shortness of breath caused by
bronchoconstriction arising from airway hyperreactivity and inflammation. Clinically,
the patient with asthma wheezes and may even become cyanotic as the breathing prob-
lem worsens. Allergic inflammation of the bronchial lining is an important causative
factor in asthma. Leukotrienes are formed during this inflammatory process, and as the
inflammation develops the bronchi become hypersensitive to a wide range of spasmo-
genic stimuli, including exercise, cold air, or even cyclooxygenase inhibitor drugs
(see chapter 8). The first-line treatment of choice for an acute asthma attack is the use
of a short-acting aerosolized β 2 sympathomimetic.β 2 agonists (e.g., terbutaline (4.60),
salbutamol (4.61)) mediate rapid bronchodilation in the lungs, and are thus a crucial
component in the initial pharmacological treatment of asthma.
Ifβ 2 mimetics have to be used more frequently than three times per week, then the phar-
macological management should also attack the inflammatory component of the disease.
This may be achieved using either anti-inflammatory steroids (see section 5.1) or long-
acting, selective leukotriene receptor antagonists (e.g., zafirlukast, see chapter 8). Since β
agonists are therapeutic for asthma, it stands to reason that βantagonists are not; in fact,
the use of βantagonists can precipitate catastrophic worsening in asthmatic patients.
Following on the clinical successes of β 2 agonists, continuing work endeavors to
identify therapeutic indications for other βagonists.β 3 agonists may have value in the
treatment of obesity, type II diabetes, and irritable bowel syndrome. Most recent work
has focused on the development of β 3 agonists for the treatment of obesity. The pre-
liminary stages of this work have been reviewed by Weyer (1999). Various aryloxy-
propanolamines and arylethanolamines have been explored as molecular platforms for
the development of β 3 agonists. However, development of several β 3 agonist compounds
has been discontinued as a result of their lack of efficacy.
NEUROTRANSMITTERS AND THEIR RECEPTORS 233