Investigation into the mechanisms by which nedocromil sodium, frusemide and bumetanide inhibit the histamine-induced itch and flare response in human skin in vivo

• Published in: Clinical and experimental allergy 2004-03, Vol.34 (3), p.450-455
• Main Authors: Willis, E. F., Clough, G. F., Church, M. K.
• Format: Article
• Language: English
• Subjects: Adult; Allergic diseases; Biological and medical sciences; bumetanide; Bumetanide - therapeutic use; chloride channels; flare; frusemide; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Furosemide - therapeutic use; Ganglia, Sensory - drug effects; histamine; Histamine - pharmacology; Histamine H1 Antagonists - therapeutic use; human skin; Humans; Immunopathology; Iontophoresis; itch; Laser-Doppler Flowmetry; Medical sciences; Nedocromil - therapeutic use; nedocromil sodium; Single-Blind Method; Skin - blood supply; Skin - innervation; Urticaria - drug therapy; Urticaria - physiopathology; Vasodilation - drug effects
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2004.01898.x

Summary Background In a previous study, iontophoresis of nedocromil sodium into human skin in vivo was shown to reduce histamine‐induced itch and flare. In asthma, the Na+/K+/2Cl− cotransporter inhibitors, frusemide and bumetanide, have been reported to have many similar actions to nedocromil sodium. Objective To compare the effects of these drugs in the histamine‐induced itch, flare and weal response in human skin in vivo and elucidate their site of action. Methods Nedocromil sodium, frusemide bumetanide and reversed osmosis water (control), were introduced by iontophoresis into the forearm skin of 10 volunteers in each of two single‐blind studies. In study 1, histamine (20 μL of 100 μm) or vehicle was injected into the area of iontophoresis 10 min later. In study 2, histamine or vehicle was injected 5 mm outside the area of iontophoresis so the flare developed over the area of iontophoresis. Itch was scored on a visual analogue scale every 20 s for 5 min, flare areas were assessed using scanning laser Doppler imaging up to 10 min and weal was assessed by planimetry at 10 min. Results In study 1, nedocromil sodium, frusemide and bumetanide reduced itch scores by 36%, 48% and 34%, respectively, and flare areas by 17%, 26% and 15% respectively (all P