Bibliographic Details
| Title: |
Antitussive activity of sigma-1 receptor agonists in the guinea-pig. |
| Authors: |
Brown, Claire, Fezoui, Malika, Selig, William M., Schwartz, Carl E., Ellis, James L. |
| Source: |
British Journal of Pharmacology; Jan2004, Vol. 141 Issue 2, p233-240, 8p |
| Subject Terms: |
ANTITUSSIVE agents, ENDORPHIN receptors, INTRAPERITONEAL injections, CITRIC acid, COUGH, GUINEA pigs |
| Abstract: |
1: Current antitussive medications have limited efficacy and often contain the opiate-like agent dextromethorphan (DEX). The mechanism whereby DEX inhibits cough is ill defined. DEX displays affinity at both NMDA and sigma receptors, suggesting that the antitussive activity may involve central or peripheral activity at either of these receptors. This study examined and compared the antitussive activity of DEX and various putative sigma receptor agonists in the guinea-pig citric-acid cough model. 2: Intraperitoneal (i.p.) administration of DEX (30?mg?kg-1) and the sigma-1 agonists SKF-10,047 (1-5?mg?kg-1), Pre-084 (5?mg?kg-1), and carbetapentane (1-5?mg?kg-1) inhibited citric-acid-induced cough in guinea-pigs. Intraperitoneal administration of a sigma-1 antagonist, BD 1047 (1-5?mg?kg-1), reversed the inhibition of cough elicited by SKF-10,047. In addition, two structurally dissimilar sigma agonists SKF-10,047 (1?mg?ml-1) and Pre-084 (1?mg?ml-1) inhibited cough when administered by aerosol. 3: Aerosolized BD 1047 (1?mg?ml-1, 30?min) prevented the antitussive action of SKF-10,047 (5?mg?kg-1) or DEX (30?mg?kg-1) given by i.p. administration and, likewise, i.p. administration of BD 1047 (5?mg?kg-1) prevented the antitussive action of SKF-10,047 given by aerosol (1?mg?ml-1). 4: These results therefore support the argument that antitussive effects of DEX may be mediated via sigma receptors, since both systemic and aerosol administration of sigma-1 receptor agonists inhibit citric-acid-induced cough in guinea-pigs. While significant systemic exposure is possible with aerosol administration, the very low doses administered (estimated <0.3?mg?kg-1) suggest that there may be a peripheral component to the antitussive effect.British Journal of Pharmacology (2004) 141, 233-240. doi:10.1038/sj.bjp.0705605 [ABSTRACT FROM AUTHOR] |
|
Copyright of British Journal of Pharmacology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Complementary Index |
