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Research ArticleArticle

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

RALPH E. GILES, JOSEPH C. WILLIAMS and MARTIN P. FINKEL
Journal of Pharmacology and Experimental Therapeutics September 1973, 186 (3) 472-481;
RALPH E. GILES
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JOSEPH C. WILLIAMS
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MARTIN P. FINKEL
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Abstract

There were differences among the beta adrenoceptor stimulants Th1165a (3,5-dihydroxy-α-{[(p-hydroxy-α-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.

Footnotes

    • Received January 8, 1973.
    • Accepted May 3, 1973.
  • © 1973 by The Williams & Wilkins Co.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 186, Issue 3
1 Sep 1973
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Research ArticleArticle

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

RALPH E. GILES, JOSEPH C. WILLIAMS and MARTIN P. FINKEL
Journal of Pharmacology and Experimental Therapeutics September 1, 1973, 186 (3) 472-481;

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Research ArticleArticle

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

RALPH E. GILES, JOSEPH C. WILLIAMS and MARTIN P. FINKEL
Journal of Pharmacology and Experimental Therapeutics September 1, 1973, 186 (3) 472-481;
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