Pharmacological studies of mabuterol, a new selective beta 2-stimulant. I: Bronchodilating effect.

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)