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  • Title: Overadditive synergism between theophylline, diprophylline and proxyphylline in tracheal smooth muscle relaxation.
    Author: Kukovetz WR, Pöch G, Holzmann S.
    Journal: Arzneimittelforschung; 1983; 33(10):1450-4. PubMed ID: 6316994.
    Abstract:
    The effects of theophylline, proxyphylline and diprophylline on cAMP-phosphodiesterase (PDE), tracheal smooth muscle tone and cAMP-levels were studied in guinea-pig tracheal preparations, and on contractile force in guinea-pig atria. Theophylline and proxyphylline inhibited tracheal PDE-activity to similar extents (I50 approximately 40 micrograms/ml) whereas diprophylline was about 5 times less effective. Half-maximum relaxation of tracheal smooth muscle was obtained with 25 micrograms/ml theophylline, 100 micrograms/ml proxyphylline and 250 micrograms/ml diprophylline. Marked rises in cAMP-levels were obtained with theophylline and, to a lesser extent with proxyphylline whereas diprophylline was almost ineffective. In combination, the relaxant effect of theophylline was over-additively enhanced by diprophylline plus proxyphylline (combination product of these three methylxanthines: Neobiphyllin) but its cAMP-increasing effect (at lower doses) was not, indicating that the potentiated relaxing action was not due to higher levels of cAMP. Diprophylline in contrast to theophylline or proxyphylline had almost no positive inotropic effect in guinea-pig atria which supports the assumption that the mechanism of tracheal smooth muscle relaxation of diprophylline is different from that of theophylline and proxyphylline and unrelated to cAMP. These findings agree with and explain the favourable anti-asthmatic effects obtained with a combination of theophylline, proxphylline and diprophylline.
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