The bronchodilating effect and other related pharmacological properties of dl-1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.-butylamino-etha nol hydrochloride (
mabuterol) were studied in comparison with those of
isoprenaline (
isoproterenol),
salbutamol and
procaterol. In relaxing the isolated normal tracheal muscle in guinea pigs,
mabuterol was more potent than
isoprenaline and
salbutamol, and the effect seemed to be due to the activation of beta-
adrenoceptors because it was inhibited by
propranolol. In anesthetized guinea pigs,
mabuterol given i.v. was less potent but showed a longer duration of action than
isoprenaline and
salbutamol in inhibiting an increase in the bronchial resistance induced by
acetylcholine,
histamine and
serotonin. When given intraduodenally, it was 1.9-7.8 times more potent than
isoprenaline and
salbutamol. In conscious guinea pigs,
mabuterol given subcutaneously was less potent than
isoprenaline and
salbutamol in experimental
asthma induced by
acetylcholine,
histamine and
antigen, but 26-102 times more potent than the reference
bronchodilators when given orally. Chronic oral treatment of
mabuterol showed no significant change in the inhibitory effect on the experimental
asthma and no development of tolerance was observed. In the maximum increase in the heart rate in conscious guinea pigs,
mabuterol given orally was less potent than
isoprenaline and
salbutamol. Calculation of the selectivity ratio of the drugs for the bronchial muscle vs. cardiac muscle indicated that
mabuterol was about 7.4 times more selective for the bronchial muscle than
salbutamol.(ABSTRACT TRUNCATED AT 250 WORDS)