Original article
The effect of theophylline and enprofylline on allergen-induced bronchoconstriction

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Abstract

The effect on the allergen-induced immediate and late bronchoconstriction of theophylline and enprofylline (3-propylxanthine), a new xanthine derivative with negligible ability to antagonize adenosine, was studied in nine patients with asthma. The patients were challenged three times at weekly intervals with the same dose of allergen. FEV1 and SGaw were followed up to 6 hours after challenge. The drugs were administered intravenously. Placebo was always administered on the first occasion. Theophylline and enprofylline were administered on test days 2 and 3 with a double-blind, randomized crossover technique. One hour before the allergen challenge, a loading dose was administered during 60 minutes followed by a constant infusion during 6 hours. The loading infusion was 7.2 mg/kg of theophylline and 2.7 mg/kg of enprofylline. The maintenance dose was 74 mg/hr and 71 mg/hr, respectively. Both theophylline and enprofylline caused a minor initial bronchodilatation. Theophylline and enprofylline slightly but significantly attenuated the immediate bronchoconstricting reaction after allergen inhalation. Theophylline and enprofylline had a significant attenuating effect on the late bronchial reaction. The mean plasma level of theophylline was 0, 10.8, 10.5, and 10.5 mg/L at 0, 1, 4, and 7 hours after the start of the loading infusion, respectively. The corresponding mean plasma levels of enprofylline were 0, 2.6, 2.7, and 2.7 mg/L. Theophylline and enprofylline caused headache in one patient. Two patients developed nausea and vomiting during the enprofylline infusion. The present data suggest that adenosine receptor antagonism may not be the main mode of action of xanthines in inhibiting bronchoconstriction after single dose antigen challenge.

References (43)

  • T.W. Rall

    The xanthines

  • C Londos et al.

    Subclasses of external adenosine receptors

  • D Van Calker et al.

    Adenosine regulates via two different types of receptors the accumulation of cyclic AMP in cultured brain cells

    J Neurochem

    (1979)
  • C.G.A. Persson

    The pharmacology of antiasthmatic xanthines and the role of adenosine

  • E Lunell et al.

    A novel bronchodilator xanthine apparently without adenosine receptor antagonism and tremorogenic effect

    Eur J Respir Dis

    (1983)
  • C.G.A. Persson et al.

    Seizure activity in animals given enprofylline and theophylline, two xanthines with partly different mechanisms of action

    Arch Int Pharmacodyn Ther

    (1982)
  • K.E. Andersson et al.

    Xanthine induced increase of plasma free fatty acids and natriuresis in man may reflect adenosine antagonism

    Eur J Clin Pharmacol

    (1984)
  • N Johannesson et al.

    Relaxation of lower esophageal sphincter and stimulation of gastric secretion and diuresis by antiasthmatic xanthines. Role of adenosine antagonism

  • E Vinge et al.

    Effects on aggregation of human platelets of two xanthines and their interactions with adenosine

    Acta Physiol Scand

    (1984)
  • C.G.A. Persson et al.

    Positive inotropic and chronotropic effects and coronary vasodilation in vitro by two antiasthmatic xanthines with different abilities to antagonize adenosine

    J Cardiovasc Pharmacol

    (1983)
  • E Lunell et al.

    Intravenous enprofylline in asthma patients

    Eur J Respir Dis

    (1984)
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