Role of opioidergic and serotonergic mechanisms in cough and antitussives

This paper provides an overview of our current understanding of the serotonerg Systemic administration of 8-OH-DPAT, at doses of 0.1 and 0.3mg/kg, ip, markedly reduced the number of coughs in rats in a dose-dependent manner. The antitussive effects of 8-OH-DPAT, dihydrocodeine and dextromethorphan were significantly reduced by pretreatment with methysergide, but not with ketanserin. Therefore it is possible to speculate that 5-HT1 receptors, in particular the 5-HT1A receptors, may be more important than others with respect to the effect of antitussive drugs. DAMGO, a selective mu-opioid receptor agonist, and U-50,488H, a highly selective delta-opioid receptor agonist, have potent antitussive effects when administered either icy or ip. However, we did not observe a cough-depressant effect of DPDPE, a selective delta-opioid receptor agonist. These results indicate that the antitussive effects of opioids are mediated predominantly by mu- and kappa-opioid receptors. On the other hand, naloxonazine, a selective mu(1)-opioid receptor antagonist, had no effect on the antitussive effects associated with icy DAMGO. These results indicate that mu(2)- rather than mu(1)-opioid receptors are involved in mu-opioid receptor-induced antitussive effects. Antitussive effects of dextromethorphan and noscapine were significantly and dose-dependently reduced by pretreatment with rimcazole, a specific antagonist of sigma sites. However, rimcazole did not have a significant effect on the antitussive effect of morphine. These results suggest that sigma sites may be involved in the antitussive mechanism of non-narcotic antitussive drugs. (C) 1996 Academic Press Limited.