title: Effects of topically delivered benzamil and amiloride on nasal potential difference in cystic fibrosis.
abstract: The raised nasal transepithelial potential difference (PD) in cystic fibrosis (CF) reflects accelerated active transport of Na+, and is inhibited by topical administration of the Na+ channel blocker, amiloride. The aim of this study was to investigate the dose-effect and time course of topically administered Na+ conductance inhibitors to inhibit nasal PD, including benzamil, an analog of amiloride. We measured the magnitude of drug inhibition of Na+ transport [percent inhibition of baseline PD (DeltaPD%)] and duration of inhibition of PD, defined as the time when drug inhibition of PD had recovered by 50% (effective time = ET50). Amiloride [10(-)3 M (n = 16), 3 x 10(-)3 M (n = 9), 6 x 10(-)3 M (n = 7), 10(-)2 M (n = 3)] or benzamil [1.7 x 10(-)3 M (n = 7), and 7 x 10(-)3 M (n = 5)] were administered to the nasal surface via an aerosol generated by a jet nebulizer and a nasal mask. The concentration-dependent magnitude (DeltaPD%) of inhibition was similar for amiloride and benzamil ( approximately 67- 77%), whereas the duration of inhibition (ET50) was about two-and-a-half times longer after benzamil administration as compared with equivalent concentrations of amiloride [1.6 +/- 0. 06 versus 4.5 +/- 0.6 h (ET50 +/- SEM), at 6-7 x 10(-)3 M]. In vitro studies of cultured normal nasal epithelia demonstrated directly that benzamil induced an approximately 2-fold more prolonged inhibition of active Na+ transport than amiloride. These data suggest aerosolized benzamil is a candidate long-duration Na+ channel blocker for CF.
authors.affiliation: Cystic Fibrosis Working Group and Selbst. Funktionsbereich Allergologie und Pneumologie der Justus Liebig Universitäts-Kinderklinik, Giessen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Hofmann
authors.forename: M J
authors.initials: MJ
authors.lastname: Stutts
authors.forename: A
authors.initials: A
authors.lastname: Ziersch
authors.forename: C
authors.initials: C
authors.lastname: Rückes
authors.forename: W M
authors.initials: WM
authors.lastname: Weber
authors.forename: M R
authors.initials: MR
authors.lastname: Knowles
authors.forename: H
authors.initials: H
authors.lastname: Lindemann
authors.forename: R C
authors.initials: RC
authors.lastname: Boucher
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000336:Aerosols; D000584:Amiloride / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000503:physiopathology*; D004848:Epithelium / Q000503:physiopathology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D009297:Nasal Mucosa / Q000503:physiopathology*; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000187:drug effects
chemical_list: D000336:Aerosols; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C013407:benzamil; C047088:phenylamil; D000584:Amiloride