Some Problems Encountered in the Evaluation of New Bronchodilating β-Adrenoceptor Agonists

Abstract

A series of phenylethanolamine derivatives were examined with respect to their bronchospasmolytic effect and their ability to depress the contractions of the soleus muscle in cat and guinea pig. One group of compounds including D2343 (1-(4-hydroxyphenyl)-2-[1,1-dimethyl-3-(2-methoxyphenyl) propylamino]-ethanol hydrochloride), a new .beta.2-adrenoceptor agonist, was more effective in combating bronchospasm induced by histamine than in depressing the contractions of the soleus muscle in anesthetized cat. This difference disappeared when serotonin was used to induce bronchospasm. Terbutaline antagonized histamine and serotonin equally well. Experiments in vivo and in vitro with guinea pigs gave ambiguous results. Slowly developing effects was a common feature of the compounds showing the apparent effect separation. None of the available .beta.-adrenoceptor agonists appears to distinguish between the adrenoceptors in the airway smooth muscle mediating bronchial relaxation and those in the skeletal muscle associated with tremor.