[Possible role of sigma-receptors in the regulation of cough reflex, gastrointestinal and retinal function].
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.
Kamei
J
J
Department of Pathophysiology & Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
D000818:Animals; D000897:Anti-Ulcer Agents; D000996:Antitussive Agents; D002227:Carbazoles / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D010423:Pentazocine / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D010620:Phenazocine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000502:physiology; D012164:Retinal Diseases / Q000188:drug therapy
D000897:Anti-Ulcer Agents; D000996:Antitussive Agents; D002227:Carbazoles; D006146:Guanidines; D008024:Ligands; D016194:Receptors, N-Methyl-D-Aspartate; D017480:Receptors, sigma; C012134:SK&F 10047; C034931:rimcazole; D010620:Phenazocine; D006220:Haloperidol; C050232:1,3-ditolylguanidine; D010423:Pentazocine