Pharmacological studies of 1-(2-chloro-4-hydroxyphenyl)-2-t-butylaminoethanol (HOKU-81), a new bronchodilator. 1st Communication: Bronchodilator and cardiovascular actions.

Bronchodilating action and influence on the cardiovascular system of 1-(2-chloro-4-hydroxyphenyl)-2-t-butylaminoethanol (HOKU-81), which is one of metabolites of tulobuterol obtained from rat urine, were examined using the isolated tracheae and atria of guinea pigs in vitro and dogs in vivo in comparison with those of the parent drug, i.e., tulobuterol isoprenaline, salbutamol and other reference bronchodilators. HOKU-81 was approximately 8 times more potent than tulobuterol, approximately twice as potent as salbutamol, and approximately as potent as isoprenaline in relaxing effect on the isolated tracheal smooth muscle preparation of guinea pigs. This effect of HOKU-81 seems to be due to direct action on the adrenergic beta-receptor. In anaesthetized dogs, bronchodilating effect of HOKU-81 was much more potent than that of tulobuterol and was approximately as potent as that of salbutamol when administered i.v., and its effect lasted for many hours. When administered orally, the duration of bronchodilating effect of HOKU-81 was almost as long as that of salbutamol. The cardiac stimulating effect of HOKU-81 examined in the isolated guinea pig artia and in anaesthetized dogs was weaker than those of isoprenaline and salbutamol, though stronger than that of tulobuterol. In the present studies in vitro as well as in vivo, the selectivity ratio of HOKU-81 for beta-adrenoceptors in the tracheal smooth muscle vs. those in the right atrial muscle was the largest of all the bronchodilators used.