Agonists sigma receptors

If PCP produces its multitude of effects by activating PCP (sigma) receptors, then chronic exposure to agonists should elicit the development of tolerance. Tolerance to plasma prolactin suppression by PCP is observed in rats following daily administration for 28 days (Quirion et al. 1982). Chronic PCP treatment has been also shown to reduce the number of PCP sites (receptors) in rodent brains (Quiriun et al. 1983). Behavioral studies have documented the development of tolerance to and dependence on PCP (Balster and Woolverton 1980 Flint and Ho 1980). A tolerance syndrome develops in humans, in which the user is compelled to increase his intake of drug (Jain et al. 1977). 

It has been proposed, on the basis of observations made using the benzo-morphan derivative (MR 2034) (8), that all kappa agonists may cause undesired dysophoria and even psychotomimesis in man [27]. Benzomorphans such as MR 2034 with affinity for sigma receptors are well-known to be associated with dysphoria. To date, there has been no report of a dose-ranging clinical study with a truly kappa selective agonist which describes the analgesic effects and the onset of dysphoric symptoms. 

Binding of [35S]GTPgammaS stimulated by (+)-pentazocine sigma receptor agonist, is abundant in the guinea pig spleen. Life Sd 67 599-603. 

Matsuno, K., Nakazawa, M., Okamoto, K., Kawashima, Y.. Mita, S., 1996. Binding properties of SA4503. a novel and selective sigma, receptor agonist. Eur. J. Pharmacol. 306, 271-279. 

It is thought that dextromethorphan and noscapine act on sigma receptors (centrally and peripherally) rather than at classic opioid receptors (Brown et al. 2004). However, the inhibitory effect of noscapine on the bradykinin B2 receptor (Ebrahimi et al. 2003) and dextromethorphan s activity at NMDA receptors (Brown et al. 2004) may also contribnte to the antitnssive activity of these drugs. Some research has been nndertaken with newer, more efficacious sigma agonists such as SKF-10,047 (Brown et al. 2004), although plenty of opportunities remain for further investigation in this area. 

Sigma receptor agonists have been associated with cough suppression. The most prominent of these is the cough-suppressant drug dextromethorphan. Given that... 

Noscapine was first isolated and characterized in the chemical breakdown and properties in 1817 under the denominatiOTi of Narcotine by Pierre Robiquet, a French chemist in Paris. Noscapine s antitussive effects appear to be primarily mediated by its sigma receptor agonist activity. Noscapine is currently under investigation for use in the treatment of several cancers and hypoxic ischemia in stroke patients. Noscapine can survive the manufacturing processes of heroin and can be found in street heroin. 

Berardi F, Ferorelli S, Abate C, Colabufo NA, Contino M, Perrone R, Tortorella V. 4-(Tetralin-l-yl)- and 4-(naphthalen-l-yl)alkyl derivatives of 1-cyclohexylpipera-zine as sigma receptor ligands with agonist sigma2 activity. J Med Chem 2004 47 2308-2317. 

Iwamoto, E.T. Locomotor activity and antinociception after putative mu, kappa and sigma opioid receptor agonists in the rat Influence of dopaminergic agonists and antagonists. J Pharmacol Exp Ther 217 451-460, 1981. 

Agonistic and Antagonistic Effects of PCP-Derivatives and Sigma Opioids in PCP Behavioral and Receptor Assays... 

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