Specific modulation of sigma binding sites by the anxiolytic drug opipramol

  title={Specific modulation of sigma binding sites by the anxiolytic drug opipramol},
  author={Gisela Holoubek and Walter E. Müller},
  journal={Journal of Neural Transmission},
Summary. The atypical anxiolytic and antidepressive drug opipramol binds with high affinity to σ1 and somewhat lower affinity to σ2 sites. After subchronic treatment, opipramol significantly down-regulated σ2 but not σ1 sites. This effect was not seen for imipramine, citalopram, and reboxetine under similar conditions. On the other hand, only imipramine reduced the number of σ1 sites. It is suggested that effects at σ2 sites are involved in the anxiolytic properties of opipramol. 
[Update Opipramol].
In view of the limited availability of (pharmacologic) treatment options for generalized anxiety disorder and particularly somatoform disorders, opipramol should be considered in the treatment of these entities.
Involvement of Chaperone Sigma1R in the Anxiolytic Effect of Fabomotizole
Results of initial in silico study showed that fabomotizole locates in the active center of Sigma1R, reproducing the interactions with the site’s amino acids common for established Sigma 1R ligands, with the ΔGbind value closer to that of agonist (+)-pentazocine in the 6DK1 binding site.
The sigma-1 antagonist BMY-14802 inhibits L-DOPA-induced abnormal involuntary movements by a WAY-100635-sensitive mechanism
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Targeting ligand-operated chaperone sigma-1 receptors in the treatment of neuropsychiatric disorders
The advances in sigma receptor research in the last decade have begun to elucidate the intracellular signal cascades upstream and downstream of sigma-1 receptors, which may enable interventions by which stress-related cellular systems can be pharmacologically controlled.
Modulation of ASIC1a function by sigma-1 receptors: Physiological and pathophysiological implications
The hypothesis presented is that sigma receptor activation inhibits ASIC1a function and ASIC1A-induced [Ca]i elevations during acidosis and ischemia, which may be a mechanism by which sigma ligands provide neuroprotection following stroke.
Consecutive Controlled Case Series on Effectiveness of Opipramol in Severe Sleep Bruxism Management—Preliminary Study on New Therapeutic Path
A single 100 mg dose of opipramol at bedtime seems to positively affect the reduction of SB in otherwise healthy individuals diagnosed with severe SB, however, the subject requires further research on a larger population including a control group.
Sigma nonopioid intracellular receptor 1 mutations cause frontotemporal lobar degeneration–motor neuron disease
The objective was to identify the causative gene in an FTLD‐MND pedigree with no mutations in known dementia genes.
Opipramol Improves Subjective Quality of Sleep the Night Prior to Surgery: Confirmatory Testing of a Double-Blind, Randomized Clinical Trial
Opipramol may be used as a premedication in the evening prior to surgery if the primary target is an impact on the experienced quality of sleep.


[3H]opipramol labels a novel binding site and sigma receptors in rat brain membranes.
Because certain of these drugs are more potent at the haloperidol-resistant opipramol site than in exerting any other action, it is possible that this opipramsol-selective site may mediate their therapeutic effects.
Rat cortical sigma receptors differentially regulated by pentazocine and haloperidol
Findings indicate that rat cortical sigma receptors are differentially regulated by pentazocine and haloperidol.
The Potential Contribution of Sigma Receptors to Antidepressant Actions
The search for drugs that combined the potent analgesic effect of morphine with a negligible abuse potential eventually led to the synthesis of pentazocine and cyclazocines, and it was found that the analgesic effects of these drugs were combined with dysphoric effects that were dose-related, the morphine-like effects being most pronounced at low doses and the dysphoric-hallucinogenic effects at high doses.
Regulation of sigma receptors and responsiveness to guanine nucleotides following repeated exposure of rats to haloperidol: further evidence for multiple sigma binding sites.
Findings suggest a marked plasticity in (+)-3-PPP/sigma receptor binding activity in rat brain and contrast, [3H]DTG binding sites expressed neither sensitivity to the repeated exposure to haloperidol nor to guanine nucleotides, suggesting a distinction between DTG and (+-3- PPP binding sites in rat head.
Opipramol for the Treatment of Generalized Anxiety Disorder: A Placebo-Controlled Trial Including an Alprazolam-Treated Group
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.
The functional sensitisation of sigma receptors following chronic selective serotonin reuptake inhibitor treatment.
The antidepressant-like effect induced by sigma(1)-receptor agonists and neuroactive steroids in mice submitted to the forced swimming test.
It was observed that local modifications in progesterone levels are directly related to the changes of in vivo sigma(1)-binding, which may be of major importance in view of the therapeutic use of selective sigma (1)-agonists in depression.