Isbufylline, a new xanthine derivative, inhibits airway hyperresponsiveness and airway inflammation in guinea pigs.
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.
Manzini
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Instituto Farmacobiologico Malesci, Pharmacology Department, Florence, Italy.
Perretti
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Abelli
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Evangelista
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Seeds
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D015056:1-Methyl-3-isobutylxanthine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000109:Acetylcholine / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D001993:Bronchodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002211:Capsaicin / Q000494:pharmacology; D003911:Dextrans; D004417:Dyspnea / Q000139:chemically induced / Q000517:prevention & control*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D010047:Ovalbumin / Q000633:toxicity; D010972:Platelet Activating Factor / Q000494:pharmacology
D001993:Bronchodilator Agents; D003911:Dextrans; D010972:Platelet Activating Factor; C015219:fluorescein isothiocyanate dextran; D006632:Histamine; D010047:Ovalbumin; C058878:isbufylline; D016650:Fluorescein-5-isothiocyanate; D000109:Acetylcholine; D000420:Albuterol; D002211:Capsaicin; D015056:1-Methyl-3-isobutylxanthine