Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper provides an overview of our current understanding of the serotonergic and opioidergic mechanisms of cough and antitussives. Systemic administration of 8-OH-DPAT, at doses of 0.1 and 0.3 mg/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 kappa-opioid receptor agonist, have potent antitussive effects when administered either icv 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 icv DAMGO. These results indicate that mu 2- rather than mu 1-opioid receptors are involved in mu-opioid receptor-induced antitussive affects. 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.
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PMID:Role of opioidergic and serotonergic mechanisms in cough and antitussives. 923 74

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.
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PMID:[Mechanisms of central antitussives]. 972 82

The cough and emetic reflexes involve a synchronized firing of motor neurones involved in respiratory control. Tachykinin NK1 receptor antagonists and 5-HT1A receptor agonists are examples of centrally acting drugs that reduce cough and emesis. In the present studies, therefore, we examined the possibility that other classes of drugs known to reducing cough have anti-emetic properties to prevent emesis induced by diverse challenges. We examined the potential of codeine (1-10 mg/kg), baclofen (1-10 mg/kg), scopolamine (0.3-10 mg/kg), diphenhydramine (1-10 mg/kg), imperialine (1-30 mg/kg) and verticine (0.3-3 mg/kg) to inhibit emesis induced by nicotine (5 mg/kg, s.c.), copper sulphate (120 mg/kg, intragastric), and provocative motion (4 cm horizontal displacement, delivered at 1 Hz) in Suncus murinus (house musk shrew). Only codeine had broad inhibitory properties (P<0.05) to antagonize emesis induced by all challenges with ID50 values ranging from 1.2 to 2.3 mg/kg. Baclofen antagonized emesis induced by nicotine (maximum reduction was 44.9%, P<0.05) and motion (maximum reduction was 97.3%, P<0.01), but potentiated copper sulphate-induced emesis (maximum potentiation was 73.0%, P<0.05). Scopolamine antagonized copper sulphate-induced emesis (maximum reduction was 61.2%, P<0.05) and imperialine antagonized nicotine-induced emesis (maximum reduction was 30.2%, P<0.01), but verticine potentiated motion-induced emesis (maximum potentiation was 60.0%, P<0.05). Diphenhydramine did not significantly reduce emesis induced by any of the challenges (P>0.05). In conclusion, codeine has broad inhibitory anti-emetic actions but a known ability to reduce coughing does not necessarily predict broad inhibitory anti-emetic properties.
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PMID:Action of anti-tussive drugs on the emetic reflex of Suncus murinus (house musk shrew). 1725 64