Abstract
This paper provides an overview of our current understanding of the role of σ-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 σ-receptor ligands was significantly reduced by pretreatment with haloperidol or rimcazol, a specific antagonist of σ-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 σ-receptors may be involved in the antitussive mechanism of nonnarcotic antitussive drugs. Selective σ-receptor ligands such as (+)SKF-10, 047, DTG and (+)pentazocine elicit a potent protection against gastric and duodenal ulcers. Ulcerprotective activity of σ-receptor ligands may be related to their stimulating effect on bicarbonate secretion through interaction with σ-receptors in the gastrointestinal mucosa. Activation of σ-receptors in retina protect retinal cells against glutamate-induced neurotoxicity. It is possible that σ-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.
