Bronchoprotection in conscious guinea pigs by budesonide and the NO-donating analogue, TPI 1020, alone and combined with tiotropium or formoterol.

British Journal of Pharmacology
Dawn L TurnerKenneth J Broadley

Abstract

Inhaled corticosteroids, anticholinergics and β₂-adrenoceptor agonists are frequently combined for treating chronic respiratory diseases. We examine the corticosteroid, budesonide, and novel NO-donating derivative, TPI 1020, against histamine- and methacholine-induced bronchoconstriction and whether they enhance the β₂-adrenoceptor agonist formoterol or muscarinic antagonist tiotropium in conscious guinea pigs. Dunkin-Hartley guinea pigs received inhaled histamine (3 mM) or methacholine (1.5 mM) and specific airway conductance (sG(aw)) was measured before and 15 or 75 min after treatment with budesonide, TPI 1020, tiotropium or formoterol alone or in combinations. Formoterol (0.7-10 µM) and budesonide (0.11-0.7 mM) inhibited histamine-induced bronchoconstriction and tiotropium (2-20 µM) inhibited methacholine-induced bronchoconstriction by up to 70.8 ± 16.6%, 34.9 ± 4.4% and 85.1 ± 14.3%, respectively. Formoterol (2.5 µM) or tiotropium (2 µM) alone exerted small non-significant bronchoprotection. However, when co-administered with TPI 1020 0.11 mM, which alone had no significant effect, there was significant inhibition of the bronchoconstriction (45.7 ± 12.2% and 79.7 ± 21.4%, respectively). Co-administering budesonide (0.11 mM...Continue Reading

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Citations

Jun 26, 2015·Expert Opinion on Emerging Drugs·Christian G WestergaardVibeke Backer
Sep 29, 2020·Journal of Experimental Pharmacology·Paola RoglianiLuigino Calzetta
Dec 19, 2019·Pharmacological Reviews·M G MateraM Cazzola
Apr 25, 2021·The Veterinary Clinics of North America. Exotic Animal Practice·María Ardiaca GarcíaVladimír Jekl

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