Zolpidem base & Uses.

[Ham-milton]

Cruise through Erowid, the majority seem to mention visuals of some sort.

Not that that's a representative sampling.

 

[EvS]

I need to do more investigation, but I'm almost-almost positive it's some type of 5ht projection that's causing the visuals.

 

[mad_scientist]

I found zolpidem gives the same kind of visuals as 5HT2a agonists, but with none of the mental effects, if I had to compare it with a benzo I guess it felt most like temazepam or something? But definite visuals there, not intense but definite patterning, movement of the edges of objects etc.

Zopiclone the visuals were quite different, really creepy shit, shadows crawling up the walls and dark figures standing in the corner of the room watching you, that kind of stuff. But again none of the LSD mindset, just visuals and benzo-like intoxication.

 

[Ionisphere1299]

Zolpidem - Pharmacology not well elucidated

Hello everyone,

I just found this post today and I'm new to the thread. Anyway I have a degree in chem and am in grad school for pharmacology and have used zolpidem on and off for 12 years on my doctor's advice. I hope you are still around and posting because I could talk about this for hours.

I don't think that zolpidem's specificity at the alpha subunit of GABAa receptors explains its pharmacology well. One poster was curious about affinity for 5-HT2 as this is the mechanism for many hallucinogenic drugs.

I will offer an alternative hypothesis. I believe zolpidem actually may have an opioid mechanism of action. Nitrazepam and temazepam display strong affinity for GABAa receptors, but less selective than zolpidem. Empirically, it has been demonstrated that both of the aforementioned BZD's interact with the mu-receptor. I modestly propose that zolpidem may interact with mu-, delta, kappa- or sigma- receptors. An action on kappa or sigma may explain the hallucinogenic, dare I say, psychotomimetic effects of zolpidem.

Radioligand binding has showed no such thing, as the people administrating the test were happy to see that it was GABA-ergic.

I know very much the hallucinogenic and thought-altering effects of this drug. I had an insurgence of this curiosity, as this week, another doctor decided that I should be on it.

As far as chemical architecture between zolpidem and BZD's, if you look at open-ring forms in either, or vice-versa (as I have), you may come up with all kinds of prospective speculation. To an extent, sometimes little of it is truly applicable in chemistry; one bond has been known to change everything.

As a chronic insomniac I have been less than impressed with zopiclone and, to a lesser extent, zaleplon.

I would be anticipatory in hearing if anyone has any more information on the zolpidem-BZD dichotomy chemically or pharmacologically. I'll say it again, an action on GABAa alpha 1 subunit just doesn't explain it!

 

[Hammilton]

their mu affinities are almost nothing.

The visuals effects are almost certainly mediated through a mechanism similar to Gaboxadol (THIP). No apparent 5HT2a affinity (never saw something that showed that it didn't) and if it has opioid receptor affinity, it's practically nothing.

has no similarity to kappa or sigma agonists (not that sigma is a opioid receptor).

 

[MurphyClox]

Indeed much speculation, although it sounds reasonable to me in the first place... Interestingly, there are no much other affinities studied with zolpidem (and alike) except for the GABAergics. Why?! ...(or do I miss a publication here? Why do you think that µ-affinity is almost nothing, Hammilton? Personal experience or have you read it somewhere?).

Murphy

 

[MurphyClox]

...some evidence for possible GABA/5HT-receptor interaction:

"The influence of serotonin depletion on rat behavior in the Vogel test and brain 3H-zolpidem binding."
M .Nazar et al.
Journal of Neural Transmission 1999, 106(5-6), pp.355-368

Abstract

The influence of p-chlorophenylalanine (p-CPA) and 5,7-dihydroxytryptamine (5,7-DHT)-induced serotonin depletion on rat behavior as well as on zolpidem's the behavioral effects and binding to some brain areas of zolpidem, was examd. with the help of Vogel's punished drinking test and autoradiog., resp. Moreover, changes in the serotonin levels and turnover rate were studied in the forebrain and brainstem of rats pretreated with various ligands at the benzodiazepine (BDZ) receptors (midazolam, bretazenil, abecarnil, zolpidem). These drugs were given at doses shown previously to significantly disinhibit animal behavior suppressed by punishment in the Vogel test. Serotonin decrease in the frontal cortex and hippocampus after p-CPA significantly and inversely correlated with rat behavior controlled by fear in the VT. P-CPA produced an anticonflict activity in the absence of effect on spontaneous drinking, pain threshold and motility of animals. All applied benzodiazepine receptor ligands decreased the 5-HT turnover rate in the frontal cortex and hippocampus, whereas in the brainstem only abecarnil and zolpidem diminished 5-hydroxyindoleacetic acid levels. This part of the study replicated earlier data with neurotoxins and indicated that the anxiolytic-like effect of 5-HT depletion in some models of anxiety did not depend on changes in animal appetitive behavior or stimulus control. Moreover, the fact that all nonselective and selective (zolpidem) agonists of the type 1 benzodiazepine receptors seemed to produce the same anticonflict effect and decreasing 5-HT turnover indicates that this subtype of benzodiazepine receptor may be important for the interaction between brain 5-HT and GABA/BDZ systems. Accordingly, serotonin decrease enhanced the anticonflict effect of zolpidem in the Vogel test and increased 3H-zolpidem binding to the occipital cortex and substantia nigra.
Altogether, the present study provides more arguments for the role of changes in the activity of brain 5-HT innervation in the control of emotional processes. Moreover, it points to the BDZ1 receptor subtype as a possible target of interaction between brain 5-HT and GABAA/BDZ systems.

Murphy

 

[alex4king]

Aviation accidents and incidents

Aviation accidents and incidents


Worlds Weirdest Animals


Amazing Coffee Paintings Art