The pharmacological actions of the new
xanthine,
isbufylline, were evaluated in several models of
airway hyperresponsiveness and airway
inflammation in guinea pigs. At a dose (106 mumol kg-1 i.p.) providing complete protection against
acetylcholine aerosol-induced
dyspnea in the guinea pig,
isbufylline inhibited
platelet activating factor (PAF)- and
antigen-induced eosinophil infiltration into bronchoalveolar lavage fluid 24 h after challenge of normal and actively immunized guinea pigs, respectively. In addition, this dose of
isbufylline also inhibited
capsaicin-induced extravasation of
protein into bronchoalveolar lavage fluid.
Isbufylline, 4.2 mumol kg-1 i.v., significantly inhibited PAF-induced bronchial hyper-responsiveness to i.v.
histamine, without exerting evident
bronchodilator activity. On the other hand the
bronchodilator,
salbutamol, at a dose (10.4 mumol kg-1 i.p.) shown to be equieffective to
isbufylline (106 mumol kg-1 i.p.) for blocking
acetylcholine aerosol-induced
dyspnea, had no protective action against PAF- or
antigen-induced eosinophil recruitment in bronchoalveolar lavage fluid, or against
capsaicin-induced
plasma protein extravasation. Furthermore,
salbutamol (3.5 mumol kg-1) significantly potentiated
allergen-induced cell infiltration and PAF-induced bronchial hyperresponsiveness. The results suggest that
isbufylline can exert significant anti-inflammatory actions in guinea pig airways, in addition to its
bronchodilator activity. These pharmacological activities are not shared by the beta 2-adrenoceptor agonist,
salbutamol.