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β2-adrenoceptor agonists is a group of drugs that act selectively on β2-receptors in the lungs causing bronchodilation. β2-agonists are used to treat asthma and COPD, diseases that cause obstruction in the airways. The first β2-agonist isoproterenol, an unselective agonist which was discovered in the 1940s. The aim of the drug development through the years has been to minimise side effects, achieve selectivity and longer duration of action. The mechanism of action is well understood and has facilitated the development. The structure of the binding site and the nature of the binding is also well known, as is the structure activity relationship. == History == The β2-selective agonists were developed in the 20th century and are a very valuable class of drugs. In 1901 a man named Takamine was the first person to isolate the hormone adrenalin or epinephrine. In 1890 adrenalin was first given to asthma patients orally. It had little or no effect because it is metabolized in the digestive tract and is deactivated. In 1930 epinephrine was for the first time given subcutaneously and was discovered to have a positive effect on asthma.〔 When given subcutaneously adrenalin affects the whole body, giving various side effects and thus reducing the value of this treatment. The inhaled route was later tried and it gave much less adverse effects, but still had inconvenient side effects like fear, anxiety, restlessness, headache, dizziness and palpitation.〔 In 1940 isoproterenol (isoprenaline) was discovered. This compound had a similar effect as adrenalin but fewer side effects were found. In 1949 isoproterenol was used generally to treat asthma patients, given sublingually or inhaled.〔 The first pressurized metered-dose inhaler was introduced in 1956. This was much more convenient for patients than the previously used squeeze-bulb inhalers. The pressurized metered-dose inhaler technique developed rapidly in the 1970s. In 1967 it was shown that the β2-receptor was responsible for bronchodilation and this led to development of more selective drugs.〔 In 1961 orciprenaline, a longer acting β2-agonist was found, but it was not as potent as isoproterenol. Orciprenaline does not have the catechol structure which was the reason for the longer action time. In the mid-1960s, albuterol or salbutamol was discovered, followed by terbutalin and fenoterol a few years later. Albuterol and terbutaline gave fewer side effects, such as increased heart rate, than isoproterenol. The pharmaceutical company Glaxo discovered salmeterol, a long-acting β2-agonist that had bronchodilation activity for up to 12 hours. It was marketed in 1990. Formoterol, another long-acting β2-agonist, was marketed shortly after. This long duration of action made the treatment for severe asthma and COPD more convenient for the patients because it is inhaled twice a day.〔 In 2013 an extra long-acting β2-agonist, vilanterol, was marketed. Its duration of action lasts for 24 hours which should improve patients' compliance and make the treatment more convenient. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Discovery and development of beta2 agonists」の詳細全文を読む スポンサード リンク
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