[Mechanisms of central antitussives].
This paper provides an overview of our current understanding of the central mechanisms of cough and antitussives. Systemic administration of 8-OH-DPAT at doses of 0.1 and 0.3 mg/kg, i.p. markedly reduced the number of coughs in rats in a dose-dependent manner. The antitussive effect of 8-OH-DPAT, dihydrocodeine and dextromethorphan significantly was reduced by pretreatment with methysergide, but not ketanserin. Therefore, it is possible to speculate that the 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 kappa-opioid receptor agonist, have potent antitussive effects when administered either i.c. or i.p. 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 i.c.v. 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.
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
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Kamei
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D006801:Humans; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D017465:Receptors, Opioid, delta / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000996:Antitussive Agents; D002121:Calcium Channel Blockers; D004745:Enkephalins; D058786:GABA-B Receptor Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D017366:Serotonin Receptor Agonists; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D020881:Enkephalin, D-Penicillamine (2,5)-