Effect of 443c81, an inhaled mu-opioid receptor agonist in asthma.

Abstract

Stimulation of exposed C-fibre afferent nerve endings by inflammatory mediators may contribute to airway inflammation and bronchoconstriction in asthma through the release of neuropeptides from collateral nerve endings. The polar opioid peptide 443c81 is a mu-opioid receptor agonist which inhibits C-fibre activation and non-cholinergic neurally mediated bronchoconstriction in animal models. We have compared the effect of 443c81 (5 ml of a 4 mg/ml solution nebulized) four times daily for 7 days with placebo on asthma control in a double-blind parallel group study of 40 subjects with mild asthma. Twenty subjects (12 male, mean FEV1 83% predicted) received placebo and 20 (15 male, mean FEV1 91% predicted) 443c81 after a 1 week run-in. Efficacy was assessed by comparing changes from baseline values in FEV1, provocative dose of histamine causing a 20% fall in FEV1 (PD20), symptom scores, bronchodilator use and home peak flow readings. 443c81 had no acute effect on FEV1 and the mean changes in FEV1 after 1 week of treatment were not significantly different (placebo -0.9%; 443c81-3.8%). One hour after the first dose of 443c81 PD20 increased from a geometric mean of 0.88 to 1.48 mumol (mean change 0.76 doubling doses; 95% CI 0.23, 1.29) but this did not differ significantly from the change with placebo (mean difference between 443c81 and placebo 0.63 doubling doses; 95% CI -0.2, 1.5; P = 0.095). After 1 week's treatment, PD20 was similar to baseline values with 443c81 (0.78 mumol) and placebo (baseline 0.71, post-treatment 0.93 mumol).(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: I Pavord, I Hall, I Wahedna, S Cooper, A Tattersfield
• Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 24 Issue 2 Pg. 144-8 (Feb 1994) ISSN: 0954-7894 [Print] England
• PMID: 8187029 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enkephalins
• Receptors, Opioid, mu
• tyrosyl-arginyl-glycyl-4-nitrophenylalanyl-prolinamide

Topics

• Administration, Inhalation
• Adolescent
• Adult
• Aged
• Amino Acid Sequence
• Asthma (physiopathology)
• Bronchial Provocation Tests
• Bronchoconstriction (drug effects)
• Double-Blind Method
• Enkephalins (pharmacology)
• Female
• Humans
• Male
• Middle Aged
• Molecular Sequence Data
• Nerve Fibers (drug effects, physiology)
• Receptors, Opioid, mu (drug effects, physiology)