Selective inhibitors for phosphodiesterase 3 and 4 in antigen-induced increase of cough reflex sensitivity in guinea pigs.

Respiratory Medicine, Cellular Transplantation Biology, Graduate School of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan. fujimura@med3.m.kanazawa-u.ac.jp

Pulmonary pharmacology & therapeutics 2007

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Effects of the selective phosphodiesterase 3 (PDE3) inhibitor olprinone and the selective PDE4 inhibitor SB207499 were investigated on antigen-induced increase of cough reflex sensitivity and normal cough response to capsaicin in guinea pigs. Number of coughs elicited by inhalation of capsaicin (10(-8), 10(-6) and 10(-4)M) was counted 24h after an antigen challenge in actively sensitized guinea pigs, and then bronchoalveolar lavage (BAL) was performed. Olprinone (1 or 10mg/kg) or SB207499 (1 or 10mg/kg) was given twice intraperitoneally: One hour after the antigen challenge and 1h before the capsaicin provocation. SB207499, but not olprinone, significantly reduced both antigen-induced increase of cough response to inhaled capsaicin in sensitized animals and normal cough response in non-sensitized animals. SB207499, but not olprinone, also reduced the antigen-induced BAL eosinophilia. PDE4 inhibitors may be useful in treating cough associated with airway allergy via inhibiting both allergic airway inflammation and the common pathway of cough reflex.

Citation

Masaki Fujimura, Qi Liu. Selective inhibitors for phosphodiesterase 3 and 4 in antigen-induced increase of cough reflex sensitivity in guinea pigs. Pulmonary pharmacology & therapeutics. 2007;20(5):543-8