Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:[Possible role of sigma-receptors in the regulation of cough reflex, gastrointestinal and retinal function]. 1056 63

The selective kappa-opioid receptor agonist spiradoline mesylate (U62,066E), an arylacetamide, was synthesized with the intention of creating an analgesic that, while still retaining its analgesic properties, would be devoid of the, mainly mu receptor mediated, side effects such as physical dependence and respiratory depression associated with morphine. Spiradoline is highly selective for the kappa receptor with K(i) of 8.6 nM in guinea pig. Examination of the enantiomers of spiradoline, showed the (-)enantiomer to be responsible for the kappa agonist properties. Spiradoline easily penetrates the blood brain barrier, and does not seem to have any significant active metabolites. In preclinical studies, spiradoline has a short duration of action with a peak at around 30 min after administration. The analgesic properties of spiradoline are well documented in mice and rats. Antitussive properties have also been reported in rats. Furthermore, spiradoline was reported to display effects suggestive of neuroprotective properties in animal models of ischemia. In humans, spiradoline is a potent diuretic. It also produces significant sedation presumably due to its antihistamine properties. Preclinical studies have shown that spiradoline reduces blood pressure and heart rate, and has possible antiarrhythmic properties. Clinical studies did not confirm these findings. kappa Receptors inhibit dopaminergic neurotransmission. Spiradoline, given systematically to rats, produces a significant and long lasting decrease in dopamine release, and in locomotor activity. It has also antipsychotic-like effect in animal behavioral tests. At low doses spiradoline was reported to decrease tics in patients with Tourette's syndrome. Although spiradoline had promising effects in animal tests of analgesia, and a reasonably good safety profile in preliminary studies, it did not replace morphine as an analgesic. The available clinical data suggest that spiradoline produces disturbing adverse effects such as diuresis, sedation, and dysphoria at doses lower than those needed for analgesic effects. Thus, future development of spiradoline-like analgesic compounds should preferably focus on reduction of unwanted effects on the central nervous system. Spiradoline, which currently is commercially available for preclinical research, might prove useful in some psychiatric conditions and possibly as a neuroprotective agent.
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PMID:A review of the properties of spiradoline: a potent and selective kappa-opioid receptor agonist. 1284 58