HOKU-81

HOKU-81 is one of the metabolites of tulobuterol. Effects of HOKU-81 on isolated trachea and atria of guinea pigs were compared with those of various bronchodilators. HOKU-81 appears to be a potent and selective beta 2-stimulant with a slight inotropic action. 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.

Pharmacological studies of 1-(2-chloro-4-hydroxyphenyl)-2-t-butylaminoethanol (HOKU-81), a new bronchodilator. 1st Communication: Bronchodilator and cardiovascular actions.[Pubmed:7192141]

Arzneimittelforschung. 1980;30(8):1272-8.

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.

Effects of 1-(2-chloro-4-hydroxyphenyl)-t-butylaminoethanol (HOKU-81), a new bronchodilator, on isolated trachea and atria of guinea pig.[Pubmed:537270]

Jpn J Pharmacol. 1979 Aug;29(4):515-24.

Effects of 1-(2-chloro-4-hydroxyphenyl)-2-t-butylaminoethanol hydrochloride (HOKU-81), one of the metabolites of tulobuterol, on isolated trachea and atria of guinea pigs were compared with those of various bronchodilators. All test drugs abolished the resting tone of tracheal muscle completely. The potencies of test drugs which induced relaxation were in the order of: trimetoquinol greater than HOKU-81 greater than or equal to isoproterenol greater than salbutamol greater than terbutaline greater than or equal to tulobuterol greater than metaproterenol greater than clorprenaline. In acetylcholine-, histamine- or potassium-stimulated preparations, the intrinsic activities of 2-chlorophenyl derivatives were less than those of 3,4- or 3,5-dihydroxyphenyl derivatives and that of HOKU-81, 2-chloro-4-hydroxyphenyl derivative, lay between two groups. HOKU-81 showed weak positive chronotropic and inotropic actions and the potency ratio of HOKU-81 to isoproterenol was about 3/100 and less than 3/1000, respectively. Both chronotropic and inotropic actions of 2-chlorophenyl derivatives, including HOKU-81, were weak and the inotropic actions of drugs with N-t-butylamino radical were weaker than chronotropic actions. Effects of test drugs on trachea and atria were antagonized by propranolol 1 x 10(-6) or 1 x 10(-7) M. HOKU-81 appears to be a potent and selective beta 2-stimulant with a slight inotropic action.