TRP channels as therapeutic targets in airway disorders: a patent review.
BACKGROUND
Chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease, affect millions of patients worldwide. New therapeutic approaches to these conditions are urgently needed since current treatment options provide only symptomatic relief. Transient receptor potential (TRP) ion channels are emerging molecular target candidates for the development of novel, disease-modifying drugs addressing airway diseases.


METHODS
The authors review the patent literature on novel molecules targeting TRP channels (in particular TRPA1, TRPV1, TRPM8 and TRPC6) that are currently studied in clinical trials or are candidates for future clinical evaluation in the management of respiratory diseases.


CONCLUSIONS
The patent literature highlights TRPA1 and TRPV1 channels as the most advanced therapeutic targets in respiratory disorders. TRPV1 antagonists relieve cough in preclinical studies. TRPA1 antagonists not only are anti-tussive but also show efficacy in allergic asthma models. However, to date, only minimal clinical data are available regarding the effects of selective, small-molecule TRPV1 and TRPA1 blockers in respiratory disorders. Clearly, long-term clinical studies are required to confirm the expectations based on preclinical data. In conclusion, the current status of this rapidly expanding research area raises cautious optimism for TRPA1 (and possibly also TRPV1) antagonists as promising anti-tussive/anti-asthma drug candidates.
University of Ferrara, Department of Pharmaceutical Sciences, via Fossato di Mortara 17/19, 44121, Italy.
Delia
D
Preti
Arpad
A
Szallasi
Riccardo
R
Patacchini
D000818:Animals; D015195:Drug Design; D006801:Humans; D049990:Membrane Transport Modulators / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015394:Molecular Structure; D010330:Patents as Topic; D012137:Respiratory System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D019141:Respiratory System Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D012140:Respiratory Tract Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013329:Structure-Activity Relationship; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism
D049990:Membrane Transport Modulators; D019141:Respiratory System Agents; D050052:TRPC Cation Channels