[Possible role of sigma-receptors in the regulation of cough reflex, gastrointestinal and retinal function].

Abstract

This paper provides an overview of our current understanding of the role of sigma-receptors in the regulation of cough, gastrointestinal and retinal function. Systemic administration of N-(+)-allylnormetazocine ((+)SKF-10,047), 1,2-di-(2-toyl)guanidine (DTG) or pentazocine markedly reduced the number of coughs in a dose-dependent manner. The antitussive effect of these sigma-receptor ligands was significantly reduced by pretreatment with haloperidol or rimcazol, a specific antagonist of sigma-receptors. Antitussive effects of dextromethorphan and noscapine were significantly and dose-dependently reduced by pretreatment with rimcazole. However, rimcazole did not have a significant effect on the antitussive effect of morphine. These results suggest that haloperidol-sensitive sigma-receptors may be involved in the antitussive mechanism of non-narcotic antitussive drugs. Selective sigma-receptor ligands such as (+)SKF-10,047, DTG and (+)pentazocine elicit a potent protection against gastric and duodenal ulcers. Ulcerprotective activity of sigma-receptor ligands may be related to their stimulating effect on bicarbonate secretion through interaction with sigma-receptors in the gastrointestinal mucosa. Activation of sigma-receptors in retina protect retinal cells against glutamate-induced neurotoxicity. It is possible that sigma-receptor ligands may be useful as therapeutic drugs against retinal disease with ischemia-induced neuronal cell death such as retinal artery occlusion, diabetes mellitus or glaucoma.

• Authors: J Kamei
• Journal: Nihon yakurigaku zasshi. Folia pharmacologica Japonica (Nihon Yakurigaku Zasshi) Vol. 114 Issue 1 Pg. 35-41 (Jul 1999) ISSN: 0015-5691 [Print] Japan
• PMID: 10562963 (Publication Type: Journal Article, Review)

Chemical References

• Anti-Ulcer Agents
• Antitussive Agents
• Carbazoles
• Guanidines
• Ligands
• Receptors, N-Methyl-D-Aspartate
• Receptors, sigma
• SK&F 10047
• rimcazole
• Phenazocine
• Haloperidol
• 1,3-ditolylguanidine
• Pentazocine

Topics

• Animals
• Anti-Ulcer Agents
• Antitussive Agents
• Carbazoles (pharmacology)
• Guanidines (pharmacology, therapeutic use)
• Haloperidol (pharmacology)
• Humans
• Ligands
• Pentazocine (antagonists & inhibitors, pharmacology, therapeutic use)
• Phenazocine (analogs & derivatives, antagonists & inhibitors, pharmacology, therapeutic use)
• Receptors, N-Methyl-D-Aspartate (physiology)
• Receptors, sigma (antagonists & inhibitors, physiology)
• Retinal Diseases (drug therapy)