Screening of Antitussive Drugs

Introduction & the cough reflex arc

• Definition — An antitussive suppresses cough; screening a candidate means demonstrating, in a validated animal model, that pre-treatment reduces an experimentally evoked cough compared with the animal's own control response.
• Cough is a reflex — Every antitussive assay exploits the reflex arc: cough receptors (mechano/chemo-sensitive) concentrated at the tracheal bifurcation (carina) and larynx/large bronchi → vagal afferents (mainly the superior laryngeal nerve) → a medullary "cough centre" → efferents that close the glottis and drive the forced expiratory thrust.
• Two logical handles — A screen (i) induces cough by a reproducible peripheral stimulus, then (ii) quantifies how the test drug changes a defined endpoint (cough number / latency / expiratory force) versus a reference standard.
• Site-of-action discrimination — Irritant-inhalation and mechanical models detect both peripherally- and centrally-acting antitussives, whereas the superior-laryngeal-nerve model "cannot detect compounds which act on cough receptors in the bronchial area" — so it is selective for centrally active agents such as codeine.