EFFICACY OF THEOPHYLLINE AND ITS N-7-SUBSTITUTED DERIVATIVES IN EXPERIMENTALLY INDUCED BRONCHIAL-ASTHMA IN THE GUINEA-PIG

  • 1 January 1981
    • journal article
    • research article
    • Vol. 253  (2) , 301-314
Abstract
The bronchospasmolytic actions of theophylline and some of its N-7-substituted derivatives administered i.v. were studied in anesthetized guinea pigs, in which experimental bronchial asthma was induced by i.v. histamine, 5-hydroxytryptamine and bradykinin. Bronchoconstriction was measured as changes in tidal volume, airflow rate, intrapleural pressure fluctuations and respiratory frequency. Dynamic lung compliance and pulmonary resistance were computed and recorded simultaneously. Blood pressure and heart rate were recorded. Theophylline, proxyphylline, diprophylline and etophylline given alone had little effect on lung function; relatively high doses of the drugs caused a fall in blood pressure and an increase in heart rate. Acephylline infusion in relatively high doses produced a decrease of dynamic lung compliance and an increase of pulmonary resistance. Some animals died. Theophylline, proxyphylline, diprophylline and etophylline were effective in reducing the mediator-induced bronchoconstriction. Protective effects correlated considerably (r = 0.75-0.82) with the plasma concentrations. The magnitude of these protective effects increased with plasma concentration. Effective doses of proxyphylline, diprophylline and etophylline were much higher than those of theophylline. Acephylline was completely inactive in reversing the mediator-induced bronchoconstriction. At relatively high doses it increased the bronchoconstrictive effects of the mediators. Diprophylline, proxyphylline and etophylline, like theophylline, are highly effective bronchospasmolytics, but doses must be adjusted according to the derivative used. Theophylline is the most effective of the 4 compounds. The therapeutic value of acephylline in asthmatics seems doubtful.

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