Antitussive and antibronchoconstriction actions of fenspiride in guinea-pigs.
Fenspiride is a nonsteroidal anti-inflammatory agent, which we have previously shown to have an in vivo antibronchoconstrictor action in guinea 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 subjective improvement in cough in patients. We have used a conscious guinea-pig model of cough as a more definitive method to study the effect of fenspiride on capsaicin- and citric acid-induced cough. Aerosolized fenspiride (1 mg.mL-1) caused a 58% reversal of capsaicin-induced bronchoconstriction; and i.v. fenspiride (1mg.kg-1) a 45% reversal of citric acid induced bronchoconstriction. Substance P- and neurokinin A-induced bronchoconstriction were unaffected by 1 mg.kg-1 i.v. fenspiride. 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 mg.mL-1) caused a shift in the citric acid dose response curve to the right. For citric acid-induced cough, the duration of action of aerosolized fenspiride (10 mg.mL-1) was found to be 5 and 15 min post-treatment. Aerosolized capsaicin (30 microM) induced cough was also reduced by 3 and 10 mg.mL-1 aerosolized fenspiride, but no significant effect was found with 1 mg.mL-1. We conclude that aerosolized fenspiride reduces capsaicin- and citric acid-induced bronchoconstriction as well as induced cough in guinea-pigs in vivo. Whether a pathway common to both cough and bronchoconstriction is the site of action of fenspiride remains to be established. We postulate that fenspiride, acting as an antitussive and antibronchoconstrictor agent, would be beneficial in the clinical situation for those patients with hyperresponsive airways.
Laude
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EA
Dept of Medicine, University of Sheffield, UK.
Bee
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D
Crambes
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Howard
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P
D000085:Acetates; D019342:Acetic Acid; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000996:Antitussive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002211:Capsaicin; D003371:Cough / Q000139:chemically induced / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D015288:Neurokinin A; D013141:Spiro Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D013373:Substance P
D000085:Acetates; D000336:Aerosols; D000996:Antitussive Agents; D001993:Bronchodilator Agents; D013141:Spiro Compounds; D013373:Substance P; D015288:Neurokinin A; D019342:Acetic Acid; D002211:Capsaicin; C084775:fenspiride