Beta-adrenoceptor agonists and XXXX --100 years of development.

@entity1 @entity2162 @entity6410 @entity565 @entity8652 @entity1425 @entity400 @entity10453 @entity3044 @entity32769 @entity70928 @entity4183
Inhaled @entity2162 agonists are by far the most effective and safe bronchodilators currently available. They have not been surpassed by any other bronchodilating principle. The way to this position has been long and started with the first successful treatment of acute, severe @entity565 with s.c. injections of adrenaline 100 years ago. Over the years, synthetic congeners of adrenaline have been produced and tested for their pharmacological properties. During the first decades, little attention was given airway smooth muscle. The discovery of @entity3044 in 1940 was the first major step towards selective bronchodilation. This compound became a key tool for the classification of adrenoceptors into alpha and beta. Salbutamol and @entity4183 were the first to show a significant attenuation of the cardiostimulant effect and confirmed the subdivision of beta-adrenoceptors into @entity8652 and beta(2). Much effort was made to eliminate the next dose-limiting side effect, skeletal muscle @entity400 but in vain. Prolonged duration of action was achieved in three ways: with @entity32769 , an orally active @entity70928 prodrug of @entity4183 , @entity10453 , an inhaled @entity2162 agonist emerging from a purposeful research project, and @entity6410 which was found, accidentally, to have a long duration of action when inhaled. Throughout the 20th century, beta-adrenoceptor agonists have been developed and marketed as racemates. The pharmacological activity usually resides in the (R)-enantiomer. Despite claims for the opposite, there is so far no compelling evidence that the presence of the less active (S)-enantiomer is of any harm to the @entity1 . One hundred years of experience of structural modifications of @entity1425 has shown that the possibilities to modify the properties of this endogenous prototype appear to be unlimited.
