American guidelines support the use of antihistamines as a first line treatment for some causes of chronic cough. The capsaicin receptor TRPV1 is thought to be one of the primary sensory receptors for cough. We therefore sought to determine whether the antihistamine Disofrol (dexbrompheniramine maleate) could antagonise TRPV1 responses to capsaicin and resiniferatoxin and could be used to treat chronic cough. Dexbrompheniramine (100µM and 1mM) significantly ablated capsaicin and resiniferatoxin triggered activation (calcium influx) of TRPV1 permanently expressing HEK293. Dexbrompheniramine was selective since it failed to inhibit PAR2 or endothelin evoked responses. Interestingly two related antihistamines diphenhydramine and fexofenadine had negligible effect on TRPV1 activation by capsaicin. Similar results were also obtained for rat TRPV1 expressing HEK and Pro5 cells. In cultured rat dorsal root ganglia neurons, dexbrompheniramine (30μM, 100μM and 300μM) also exhibited an inhibitory effect on capsaicin evoked responses. Finally, 76 patients referred to Hull cough clinic with intractable cough were recruited and dispensed dexbrompheniramine (Disofrol) twice daily for four weeks. Dexbrompheniramine improved cough in 48 (63%) of patients. Overall the mean (standard deviation) visual analogue cough score following treatment (4.82 ± (2.6)) was significantly lower than before treatment (7.63 ± (1.42), p=<0.001). The results therefore suggest that dexbrompheniramine may inhibit TRPV1 and may be a safe and effective treatment for chronic cough.