ANTITUSSIVE AND ANTIBRONCHOCONSTRICTION ACTIONS OF FENSPIRIDE IN GUINEA-PIGS

Fenspiride is a nonsteriodal anti-inflammatory agent, which we have pr eviously shown to have an in vivo antibronchoconstrictor action in gui nea pigs. We have currently studied this action using the constrictors Substance P, neurokinin A, citric acid and capsaicin in anaesthetized guinea-pigs, Fenspiride has also been reported to produce a subjectiv e improvement in cough in patients, We have used a conscious guinea-pi g model of cough as a more definitive method to study the effect of fe nspiride on capsaicin- and citric acid-induced cough, Aerosolized fens piride (1 mg . mL(-1)) caused a 58% reversal of capsaicin-induced bron choconstriction; and iv. fenspiride (1 mg . kg(-1)) a 45% reversal of citric acid induced bronchoconstriction. Substance P- and neurokinin A -induced bronchoconstriction were unaffected by 1 mg . kg(-1) iv. fens piride. Aerosolized fenspiride (1, 3 and 10 mg . mL(-1)) administered for 4 min reduced citric acid (300 mM) induced cough, but 0.1 mg . mL( -1) was without effect. Pretreatment with aerosolized fenspiride (10 m g . mL(-1)) caused a shift in the citric acid dose response curve to t he right. For citric acid-induced cough, the duration of action of aer osolized fenspiride (10 mg . mL(-1)) was found to be 5 and 15 min post -treatment. Aerosolized capsaicin (30 mu M) induced cough was also red uced by 3 and 10 mg . mL(-1) aerosolized fenspiride, but no significan t effect was found with 1 mg . mL(-1). We conclude that aerosolized fe nspiride reduces capsaicin- and citric acid-induced bronchoconstrictio n as well as induced cough in guinea-pigs in vivo, Whether a pathway c ommon to both cough and bronchoconstriction is the site of action of f enspiride remains to be established. We postulate that fenspiride, act ing as an antitussive and antibronchoconstrictor agent, would be benef icial in the clinical situation for those patients with hyperresponsiv e airways.