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

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.