Safety by design.

Safety by design for any kind of drug requires it to act selectively on the cells which mediate the desired effect, and affect other cellular functions as little as possible. To illustrate this, the treatment of bronchial asthma was much improved during the past 20 years by the development of inhalation treatment based on drugs such as salbutamol (albuterol), a selective beta 2-adrenoceptor stimulant, and beclomethasone dipropionate, a topical anti-inflammatory steroid, from their parent physiological mediators epinephrine (adrenaline) and hydrocortisone (cortisol). Their development and that of H1- and H2-antagonists from histamine are described. From these and other sources the general conditions for safe, selective drug action and the range of drug effects that may be attained by modifying physiological mediators are deduced. This involves the identification and definition of type 1 and type 2 agonism. This analysis led to the discovery of salmaterol (salmeterol), a new uniquely long acting beta 2-adrenergic bronchodilator, by modification of salbutamol. The development, by modification of serotonin (5-hydroxytryptamine), of ondansetron, a new antiemetic for use in cancer chemotherapy, and sumatriptan, a new type of drug for treating migraine, are also described. All these new drugs are more efficacious and safer than their predecessors.