Delta-opioid receptor antagonists as a new concept for central acting antitussive drugs.

Our recent findings indicated that mu- and kappa-opioid receptors enhance each other's antitussive processes. However, delta-opioid receptors played an inhibitory role in antitussive processes mediated by the mu- and kappa-opioid receptors. We also concluded that delta(1)-opioid receptors may play an inhibitory role, whereas delta(2)-opioid receptors may play a synergistic role, in antitussive processes mediated by mu-opioid receptors. Furthermore, we clearly demonstrated that delta-opioid receptor antagonists, such as naltrindole and 7-benzylidenenaltrexone, produced potent antitussive effects. These delta-opioid receptor-mediated antitussive effects may be mediated by the antagonism of delta(1)-, but not delta(2)-opioid receptors. In this review, we study the possibility of the delta-opioid receptor antagonist as a new concept for central acting antitussive drugs.