Posted by ed_uk on June 19, 2005, at 10:11:54
In reply to What is a sigma 1 receptor ??, posted by linkadge on June 19, 2005, at 0:21:06
'Sigma sites are a type of nonopiate receptor whose role has been associated with several behaviours, including anxiety, depression, analgesia, learning processes and psychosis.'
'Sigma receptors have been implicated in psychosis, cognition, neuroprotection, and locomotion in the central nervous system.'
This may be of interest.....
(from Shawn T's neurotransmitter.net)
Escitalopram --
Escitalopram (Lexapro) is a serotonin reuptake inhibitor. The drug is the S-enantiomer of citalopram (Celexa). Fabre and Hannon (2003) have suggested that escitalopram's effects might be mediated in part by agonism at sigma-1 and sigma-2 receptors; however, further investigations are required to make a definitive conclusion.
Ravna AW, Sylte I, Dahl SG.
Molecular mechanism of citalopram and cocaine interactions with neurotransmitter transporters.
J Pharmacol Exp Ther. 2003 Oct;307(1):34-41. Epub 2003 Aug 27. [Abstract]Fabre V, Hamon M.
[Mechanisms of action of antidepressants: new data from Escitalopram]
Encephale. 2003 May-Jun;29(3 Pt 1):259-65. [Abstract]........................
Darkhorse used to take opipramol........
opipramol
Description
Potent sigma receptor ligand. Sedative, stabilizing and mood elevating properties.
'Opipramol, which, apart from a sigma-1- and 2-receptor liability, also possesses histamine-H(1)-antagonistic properties in connection with lower affinities for D(2) and 5-HT(2A) showed broad efficacy in generalized anxiety disorder and somatoform disorders. The receptor profile of opipramol and the results of studies of the selective sigma site ligands siramisine and igmesine suggest that opipramol acts pharmacologically and clinically via sigma receptors.'
'The atypical anxiolytic and antidepressive drug opipramol binds with high affinity to sigma1 and somewhat lower affinity to sigma2 sites. After subchronic treatment, opipramol significantly down-regulated sigma2 but not sigma1 sites. This effect was not seen for imipramine, citalopram, and reboxetine under similar conditions. On the other hand, only imipramine reduced the number of sigma1 sites. It is suggested that effects at sigma2 sites are involved in the anxiolytic properties of opipramol.'
'Although opipramol is structurally related to imipramine, it does not represent a tricyclic antidepressant drug as it does not inhibit the neuronal uptake of norepinephrine and/or serotonin. Unlike imipramine it is a rather potent sigma ligand with modest subclass selectivity which is similar in vitro as well as ex vivo. Opipramol is active in several behavioural paradigms indicative of anxiolytic properties at doses (1-10 mg/kg), which are also needed to occupy sigma binding sites. Somewhat higher doses (10-20 mg/kg) are needed for "antidepressant like" effects. The data allow the conclusion that interaction with sigma sites is involved in the anxiolytic and antidepressant effects of opipramol albeit a contribution of its weaker D (2)-antagonistic and 5-HT2-antagonistic properties cannot be totally be excluded.'
J Clin Psychopharmacol. 2001 Feb;21(1):59-65.
Opipramol for the treatment of generalized anxiety disorder: a placebo-controlled trial including an alprazolam-treated group.
Moller HJ, Volz HP, Reimann IW, Stoll KD.
Psychiatrische Klinik der Ludwig-Maximilians-Universitat, Munich, Germany.
Opipramol, a drug widely prescribed in Germany, is a tricyclic compound with no reuptake-inhibiting properties. However, it has pronounced D2-, 5-HT2-, and H1-blocking potential and high affinity to sigma receptors (sigma-1 and sigma-2). In early controlled trials, anxiolytic effects were revealed. However, those studies were performed before the concept of generalized anxiety disorder (GAD) was established. Because of the interesting receptor-binding profile and promising results of the early clinical trials, the authors performed a state-of-the-art placebo-controlled trial using alprazolam as an active control. Three hundred seven outpatients with GAD were included. After a 7-day single-blind placebo washout, patients were randomly assigned to receive either opipramol (final dose, 200 mg/day), alprazolam (2 mg/day), or placebo and were treated for 28 days. The efficacy of both active compounds was higher than the effects with placebo treatment. There were statistically significant differences (p < 0.05, according to the analysis of covariance) in the main outcome criterion (baseline-adjusted final means of an intent-to-treat analysis of the total scores on the Hamilton Rating Scale for Anxiety) and in secondary efficacy parameters, with global improvement of 47% for placebo and significantly more for opipramol (63%) and alprazolam (64%). Regarding safety and tolerability, no substantial differences in the number of adverse events observed between treatment groups were obvious. Sedation seemed more pronounced with alprazolam treatment than with opipramol or placebo. In this trial, it was demonstrated for the first time that opipramol, a strong but nonselective sigma site ligand, possesses anxiolytic efficacy superior to placebo in the treatment of GAD.
Seroquel also binds to sigma receptors........
'.........quetiapine, an atypical antipsychotic with high affinity for H1 and moderate affinity for sigma, alpha1, 5-HT2, alpha2 and D2 receptors.........'
Pentazocine, an opioid analgesic which tends to induce psychotic symptoms, acts as an agonist at sigma receptors. The sigma receptor may have a role in psychotic disorders. Perhaps it's not such a good thing that Lexapro acts as a sigma agonist!?
Dis Nerv Syst. 1975 Jul;36(7):404-5.
Pentazocine psychosis: a case of persistent delusions.
Blazer DG, Haller L.
A case of psychosis secondary to pentazocine is presented. The patient demonstrated hallucinations, preceptual aberrations, a distorted body image and delusional thinking. The delusional ideation persisted for a period of three weeks. Such a case of persistent delusional thinking secondary to pentazocine administration has not been reported previously.
poster:ed_uk
thread:515346
URL: http://www.dr-bob.org/babble/20050617/msgs/515449.html