Novel pharmacological targets and progression of new antitussive drugs

Cough is frequently associated with a wide array of respiratory infections, ailments and disorders. Consequently, cough is the number one symptomatic reason why people visit medical healthcare providers. Nonetheless, when cough-suppressant therapy is required by patients, many physicians are limited primarily to a single pharmacological class of antitussive agent, namely, opioids. Opioids, such as codeine, dominate the antitussive prescription market. These drugs act centrally within the CNS to attenuate cough due to a variety of causes. However, opioids often elicit significant receptor-related mu-opioid (MOP) untoward side effects such as constipation, respiratory depression, sedation, tolerance and addiction. The development of novel drugs that maintain or improve upon the antitussive efficacy of the opioids and do not possess MOP liabilities would represent a substantial improvement over currently available cough treatments. New antitussive pharmacological targets include non-MOP opioids, specifically, delta-opioid and X-opioid receptor agonists. In addition, drugs that activate the recently discovered 'opioid-like' NOP receptor also attenuate cough in various experimental models. Other interesting pharmacological approaches to inhibit cough include GABAergic-, serotonergic- and dopaminergic-receptor agonists and tachykinin, vanilloid receptor and eicosanoid antagonists. Furthermore, the importance of endogenous inflammatory mediators such as bradykinin in the genesis of cough continues to unfold. The degree to which any of these novel approaches develop as new antitussive therapies will depend on their efficacy and safety in human cough, which remains to be determined.