Sigma agonists

Slifer, B.L., and Balster, R.L. Reinforcing properties of stereoisomers of the putative sigma agonists N-allylnormetazocine and cyclazocine in Rhesus monkeys, il Pharmacol Fxp Ther 225 522-528, 1983. 

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. 

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. 

Leventer, S.M., and Johnson, K.M. Phencyclidine-induced inhibition of striatal acetylcholine release Comparisons with mu, kappa, and sigma opiate agonists. I i f e Sci 34 793-801, 1984. 

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

Young, G.A. Neistada, L. and Khazan, N. Differential neuro-pharmacological effects of mu, kappa, and sigma opioid agonists on cortical EEG power spectra in the rat. Res Commun Psvchol Psvchiatr Behav 6 365-377, 1981. 

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). 

In addition to PCP, other sigma opiate agonists, particularly SKF 10,047, accelerate striatal DA turnover. A small (+15%) but significant elevation of DOPAC levels occurs in the striatum of SKF 10,047-treated rats (128). 

Wood, P. L., Scotland, M., Richard, J. W., and Rackham, A. (1980) Actions of mu, kappa, sigma, delta and agonist/antagonist opiates on striatal dopaminergic function. J. Pharmacol. Exp. Then, 215 697-703. 

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. 

The mechanisms of action of phencyclidine and ketamine are complex (Gorelick Balster, 1995). The drugs are non-competitive antagonists at NMDA receptors, and also bind to associated phencyclidine/sigma opioid receptors. They also have agonist actions at dopamine receptors, complex interactions with both nicotinic and muscarinic acetylcholine receptors and poorly understood interactions with noradrenergic and serotonergic systems. These multiple actions may combine to produce delirium and psychotic reactions. 

Smooth muscle sarafotoxin S6c/Sigma 2000 pept./vasoactive, agonist of the ETb endothelin receptor Atractaspis engaddemis, Serpentes, Reptilia... 

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

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