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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Effects of topically delivered benzamil and amiloride on nasal potential difference in cystic fibrosis.

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.[1]

References

  1. Effects of topically delivered benzamil and amiloride on nasal potential difference in cystic fibrosis. Hofmann, T., Stutts, M.J., Ziersch, A., Rückes, C., Weber, W.M., Knowles, M.R., Lindemann, H., Boucher, R.C. Am. J. Respir. Crit. Care Med. (1998) [Pubmed]
 
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