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Central vs. peripheral sites of action of antitussive agents in anesthetized guinea pigs
Author(s) -
Chou YangLing,
Canning Brendan J
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1011.3
Subject(s) - dextromethorphan , medicine , pharmacology , lidocaine , mexiletine , baclofen , anesthesia , peripheral , cough reflex , codeine , airway , morphine , receptor , agonist
Dextromethorphan (DEX), SKF10047, codeine, DAMGO, mexiletine and baclofen have all been reported to prevent cough, in part, through direct peripheral effects on airway sensory nerves. We evaluated the ability of these drugs to modify coughing evoked by citric acid (CA) applied topically to the tracheal mucosa of anesthetized GPs. Drugs were applied topically to the tracheal mucusa (10‐100 μM) or were microinjected (0.1‐500nmol) bilaterally into nTS. CA (0.001‐2M) applied topically in ascending doses and in 100 μL aliquots evoked 13±2 coughs cumulatively (n=36). Mexiletine applied topically to the tracheal mucosa nearly abolished CA evoked coughing (3±1 coughs; n=6). None of the other drugs had any effect on cough when applied topically to the tracheal mucosa (n≤4). By contrast, all 6 drugs studied dose dependently inhibited (90‐100%) cough when microinjected bilaterally into the nTS sites of cough receptor termination (n=3‐6). Microinjection of the drugs into adjacent nTS locations was without effect on cough (n≤3). The data indicate that baclofen, DEX, SKF10047, DAMGO and codeine prevent cough receptor dependent cough by actions in the CNS and not in the periphery.