THE BRONCHODILATOR AND CARDIAC STIMULANT EFFECTS OF Th1165a, SALBUTAMOL AND ISOPROTERENOL

¹ Department of Pharmacology, Warner-Lambert Research Institute, Morris Plains, New Jersey

There were differences among the beta adrenoceptor stimulants Th1165a (3,5-dihydroxy--{[(p-hydroxy--methylphenethyl)amino] methyl}-benzyl alcohol hydrobromide; hydroxyphenylorciprenaline), isoproterenol and salbutamol in bronchodilator and cardiac stimulant potency. In vitro, the agonists were similar in potency in relaxing guinea-pig trachea but the order of potency for the chronotropic response of guinea-pig atria was isproterenol > Th1165a > salbutamol. In vivo, drugs were evaluated in both guinea pig and dog. Each of the agonists administered i.p., p.o. or by aerosol protected against histamine-induced collapse in guinea pigs; isoproterenol produced a greater tachycardia than either Th1165a or salbutamol. By mouth, salbutamol was more potent than Th1165a or isoproterenol in preventing histamine-induced collapse. In the anesthetized dog, Th1165a or salbutamol, i.p., protected against histamine-induced bronchospasm at doses which caused minimal cardiac stimulation, but isoproterenol caused a pronounced tachycardia, even at doses affording weak protection. The bronchoconstrictor effects of pilocarpine in the dog were significantly reduced by i.v. administration of each of the agonists; duration of the effect of Th1165a or salbutamol was longer than that of isoproterenol. Th1165a and salbutamol produced long-lasting bronchodilatation with less cardiac stimulation than did the shorter acting agonist isoproterenol.