{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T13:57:24Z","timestamp":1780667844894,"version":"3.54.1"},"reference-count":45,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,4,23]],"date-time":"2015-04-23T00:00:00Z","timestamp":1429747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2015,6]]},"abstract":"Background and Purpose<\/jats:title>Inhaled amiloride, a blocker of the epithelial sodium channel (ENaC<\/jats:styled-content>), enhances mucociliary clearance (MCC<\/jats:styled-content>) in cystic fibrosis (CF<\/jats:styled-content>) patients. However, the dose of amiloride is limited by the mechanism\u2010based side effect of hyperkalaemia resulting from renal ENaC<\/jats:styled-content> blockade. Inhaled ENaC<\/jats:styled-content> blockers with a reduced potential to induce hyperkalaemia provide a therapeutic strategy to improve mucosal hydration and MCC<\/jats:styled-content> in the lungs of CF<\/jats:styled-content> patients. The present study describes the preclinical profile of a novel ENaC<\/jats:styled-content> blocker, NVP<\/jats:styled-content>\u2010QBE<\/jats:styled-content>170, designed for inhaled delivery, with a reduced potential to induce hyperkalaemia.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>The in vitro<\/jats:italic> potency and duration of action of NVP<\/jats:styled-content>\u2010QBE<\/jats:styled-content>170 were compared with amiloride and a newer ENaC blocker, P552\u201002, in primary human bronchial epithelial cells (HBEC<\/jats:styled-content>s) by short\u2010circuit current. In vivo<\/jats:italic> efficacy and safety were assessed in guinea pig (tracheal potential difference\/hyperkalaemia), rat (hyperkalaemia) and sheep (MCC<\/jats:styled-content>).<\/jats:p><\/jats:sec>Key Results<\/jats:title>I<\/jats:italic><\/jats:styled-content>n vitro<\/jats:italic>, NVP<\/jats:styled-content>\u2010QBE<\/jats:styled-content>170 potently inhibited ENaC<\/jats:styled-content> function in HBEC<\/jats:styled-content> and showed a longer duration of action to comparator molecules. In vivo<\/jats:italic>, intratracheal (i.t.) instillation of NVP<\/jats:styled-content>\u2010QBE<\/jats:styled-content>170 attenuated ENaC<\/jats:styled-content> activity in the guinea pig airways with greater potency and duration of action than that of amiloride without inducing hyperkalaemia in either guinea pig or rat. Dry powder inhalation of NVP<\/jats:styled-content>\u2010QBE<\/jats:styled-content>170 by conscious sheep increased MCC<\/jats:styled-content> and was better than inhaled hypertonic saline in terms of efficacy and duration of action.<\/jats:p><\/jats:sec>Conclusions and Implications<\/jats:title>NVP<\/jats:styled-content>\u2010QBE<\/jats:styled-content>170 highlights the potential for inhaled ENaC<\/jats:styled-content> blockers to exhibit efficacy in the airways with a reduced risk of hyperkalaemia, relative to existing compounds.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13075","type":"journal-article","created":{"date-parts":[[2015,1,9]],"date-time":"2015-01-09T11:49:57Z","timestamp":1420804197000},"page":"2814-2826","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["NVP<\/scp>\u2010QBE<\/scp>170: an inhaled blocker of the epithelial sodium channel with a reduced potential to induce 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