Benzos Ethylbromazolam

[Allylbenzene]

There's also a phenethylamine accompanying ethanol in beer. Question is, is it present at relevant concentrations?
Hordenine (dimethyltyramine), a reversible MAO-B inhibitor, NRI and potentially a D2 agonist.

D2R-promoted G-protein activation was observed for hordenine, a constituent of barley and beer, with approximately identical ligand efficacy as dopamine (76%) and a Ki value of 13 μM. Moreover, hordenine antagonised D2-mediated β-arrestin recruitment indicating functional selectivity.

https://www.nature.com/articles/srep44201

One of the main sources of hordenine is germinated barley (Hordeum vulgare l.), which can release hordenine into beer during the brewing process. Several types of beer contain hordenine concentrations ranging from 1.0 to 6.3 mg/L, suggesting that beer consumption may contribute to a large proportion of dietary hordenine intake [5].

https://pmc.ncbi.nlm.nih.gov/articles/PMC9202863/

Studies, with selective irreversible inhibitors of MAO, showed that hordenine was a highly selective substrate for MAO-B of liver and that it was not deaminated by the MAO-A of intestinal epithelium.
...
These results indicate that dietary-hordenine is unlikely to be deaminated by intestinal MAO as this is predominantly MAO-A. Consequently, it is likely to be absorbed and could affect the sympathetic nervous system, by virtue of its action as an inhibitor of noradrenaline uptake.

https://pubmed.ncbi.nlm.nih.gov/2570842/

Animal study on hordenine from 2025. No D2 activity found.

Further characterization revealed monoaminergic binding sites of hordenine and found a strong binding on the serotonin and dopamine transporters, and dopamine D3, and adrenergic α1A and α2A receptor activation but no effects on GABAA receptor or glycinergic signalling.

https://onlinelibrary.wiley.com/doi/full/10.1111/adb.13305

 

[4DQSAR]

The third paper is of particular interest but it's quite often the case that models aren't always useful. I note that while hordinine supplements (100mg) are available, tachycardia and hypertension are issues. The doses used in the paper seem a lot higher. I think it IS that measuring dopamine activity (locostimulation or lack thereof) but they may have it the wrong way around.

'Ratatonia' is the nickname researchers give to the odd observation that when given many psychostimulants... the rodent models just stop moving. I don't think anyone knows why and it's unclear if they are relying on the effect or discounting it. But it's so random, it does seem an odd model to choose.

I DO appreciate the fact that hordenine cannot itself be patented although by now, I would expect someone to have tried patetenting the specific use of a compound, in this case alcohol dependence.

I think lastly we also have to realize that rodent consciousness is different from that of (most) humans. You can train rodents to consume alcohol and then you can deprive them off it and watch to see if a given compound alters phsical behavior. But I would argue that alcoholism is, at least in part, a psychological issue. Sure, you can wind up NEEDING to drink alcohol to avoid withdrawal, but it's my understanding that most people are able to get sober with appropriate support, but it's the remaining sober that's the real challange.

Has someone attempted to get a patent? I only ask because the people behind that last stufy would seem likely to have at least attempted to acquire one to claw back the costs of the research (and make more on top, obviously).

 

[Esperighanto]

Well, by all means provide references.

Becaue I spend a good few days on it although I admit it was a few years ago.

It's unclear if you are asserting all of the above to be factual, but as I have repeatedly notes, animal models are frequenctly unreliable.

If it's your own hypothesis, fine, but do say so if that is the case. There is no shame in it, I have proposed serveral hypotheses myself but was vey clear that it WAS just my hypotheses.

Would this also relate to the THIQs in peyote? There definitely appears to be some activity, likely somewhat sedative activity I thought

 

[Allylbenzene]

I note that while hordinine supplements (100mg) are available, tachycardia and hypertension are issues.

It used to be available in unbranded powder form in the UK, I've just looked and can't see anything except branded capsules.

Regarding effects, as a norepinephrine reuptake inhibitor, reversible MAO-Bi, D2 agonist and vasoconstrictor this might explain any tachycardia / hypertension.

The effects of hordenine are similar to other adrenergics (ephedrine, yohimbe, etc.). Compared to ephedrine or yohimbe, it’s often said to be smoother, not jittery or jolting. It can produce mild euphoria. The stimulant effect is very smooth and mild, and can smooth out the rough edges of things like caffeine. It’s a good addition to other stimulants, being somewhat mild on it’s own, but altering the effects of other stimulants often in a very positive way.

50 MG: very mild, slight tingling sensations, very mild stimulation. This is probably the lower dose a person could feel.
100 MG: mild tingling sensations, mild stimulation, very mild euphoria similar to small doses of caffeine.
200 MG: mild tingling sensations, moderate stimulation, mild euphoria similar, general sense of wellbeing. About the potency of 1 cup of coffee.

 

[Allylbenzene]

Would this also relate to the THIQs in peyote? There definitely appears to be some activity, likely somewhat sedative activity I thought

The cactus THIQs likely contribute along with the PEAs (eg 3,4-dimethoxyPEA, hordenine, 3-methoxytyramine) either directly or by inhibiting/inducing enzymes (ALDH, MAO, possibly SSAO, xanthine oxidase, aldehyde oxidase) which influence mescaline's metabolism, particularly the formation of it's immediate aldehyde metabolite and any subsequent products that might form from it.

The cactus flavonoids can also contribute relevant enzyme inhibiton/induction.

Re xanthine oxidase and aldehyde oxidase:

Xanthine oxidase also performs enzyme actions on several aldehydes creating carboxylic acids, an action also performed by aldehyde oxidase and aldehyde dehydrogenase (ALDH).

Fwiw here's Trouts notes on cactus PEAs:

structural tables; phenethylamines – Trout's Notes

sacredcacti.com

Btw @Esperighanto, if you're going to make some THIQs as you alluded to in another post, I wouldn't use PEA, MDPEA or dopamine as precursors since the associated THIQs are likely toxic or unsafe (eg 1-MeTIQ, MDTHIQ, salsolinol).

On the THIQ theme, another interesting one is cinnamolaurine found in sassafras and some cinnamon species, it's based on MDPEA. It's reported to contribute uplifting euphoric effects (extracted via A/B giving a full-spectrum extract). It's similar in structure to the THIQ higenamine which is based on dopamine.

Higenamine is a natural compound that can be extracted from plants such as Aconitum and Annona squamosa. It has been used in traditional Chinese medicine to treat a variety of cardiac disorders (e.g., bradycardia, arrhythmia, heart failure). Modern studies have shown that higenamine possesses a variety of pharmacological properties, such as antioxidant properties, improvement of cellular energy metabolism, anti-apoptosis, and improving erectile dysfunction. Higenamine acts as a non-selective β-agonist, activating both β1- and β2-adrenergic receptors.

A Narrative Review on Higenamine: Pharmacological Properties and Clinical Applications - PMC

Background: Higenamine, a bioactive alkaloid derived from plants such as Aconitum and Annona squamosa, has been traditionally used in Chinese medicine for treating heart diseases like bradycardia, arrhythmia, and heart failure. It exhibits multiple ...

pmc.ncbi.nlm.nih.gov

 

[4DQSAR]

Well, it's your body, it's your choice.

I look forward to reading your trip reports.

Didn't Shulgin actually publish 'The Simplee Plant Isoquinolines'? I don't know much about it beyond never having seen anyone refer to it as a source. It may even be a freed .PDF somewhere online, but I would assume it to be quite complete, given that it's some 624 pages.

 

[Allylbenzene]

Didn't Shulgin actually publish 'The Simplee Plant Isoquinolines'?

He did yes.
On the alcohol theme, it's possible adenosine is involved in alcohols effects - via reuptake inhibiton.
https://www.nature.com/articles/s41598-017-12689-6
https://pmc.ncbi.nlm.nih.gov/articles/PMC2940831/

Also glutamate antagonism
https://www.sciencedirect.com/science/article/abs/pii/S0006899304014763

What do you make of it? I know you've made it very clear that animal models aren't always reliable.

Well, by all means provide references.

Becaue I spend a good few days on it although I admit it was a few years ago.

It's unclear if you are asserting all of the above to be factual, but as I have repeatedly notes, animal models are frequenctly unreliable.

If it's your own hypothesis, fine, but do say so if that is the case. There is no shame in it, I have proposed serveral hypotheses myself but was vey clear that it WAS just my hypotheses.

I wrote that based on these papers (see below) and the scenario of drinking large amounts of alcohol. The increased acetaldehyde from ethanol could sufficiently occupy/inhibit ALDH2 allowing some tetrahydropapaveroline to form from DA/dopaldehyde condensation (alongside salsolinol). Taking cocaine would further promote tetrahydropapaveroline & salsolinol formation since it's DRI activity would increase dopamine and it's metabolite dopaldehyde.

Potentially serotonin would participate in the pictet-spengler formation too alongside dopamine...

On Salsolinol's activity:
https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2013.00052/full
https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2021.675061/full
https://pmc.ncbi.nlm.nih.gov/articles/PMC5117487/
https://link.springer.com/rwe/10.1007/978-3-030-67928-6_52-1

On tetrahydropapaveroline formation from DA and DOPAL and inhibition of tyrosine hydroxylase = reduced DA synthesis
https://pubmed.ncbi.nlm.nih.gov/9572583/
https://www.ncbi.nlm.nih.gov/pubmed/20729865

Possible DRI
https://pubmed.ncbi.nlm.nih.gov/9572583/

To summarise...

It's possible that drinking large amounts of alcohol causes GABA-A, non-NMDA glutamate antagonism and pro-adenosine (calming) effects alongside potential active metabolites with opiate & dopamine effects (salsolinol & tetrahydropapaveroline).

Plus whatever potential beta carboline is formed from the pictet-spengler condensation of serotonin & acetaldehyde. If acetaldehyde reaches dopamine (making salsolinol), surely it can reach serotonin?

If the (binge) drink of choice is barley-derived beer, then barleys phenethylamine (hordenine) would contribute D2 agonism, MAO-B inhibiton & increased norepinephrine (via norepinephrine reuptake inhibiton).

So, alcohols direct activity whilst also acting as a psuedo/pro-drug for active tetrahydroisoquinolines and possible tetrahydro-β-carbolines (more likely if taking SSRIs?).

 

[50shadesofDave]

I've enjoyed reading this thread, I was thinking about this substance just last night, after looking at wedinos, I haven't got a clue what your on about though, but please crack on.

Can I ask why the need to keep fucking around with a family of drugs everyone was perfectly happy with?
I get the r/c bit, sell it in the 24hr garage till it gets banned, do these gangs think we won't notice? I could have died last year with those ropey diaz that I honestly think had nitazenes in, due to the condition I was in, teeth grinding and broke two, sweating heavily, locked to the couch with my cats staring at me from outside the room, I took them to try and fend off a seizure due to c/t 30mg diaz.

Shit benzo scene at the moment overall and I'm trying to build enough for a taper.

Anyway as always, take care folks.

 

[Allylbenzene]

Shit benzo scene at the moment overall and I'm trying to build enough for a taper.

Try agmatine, it's OTC and cheap. I wrote about it in an earlier post. Agmatine reduces the stimulating effects of adrenaline and prevents glutamate based excito-toxicity. It also increases the bodies production of allopregnanolone which enhances the effect of GABA (see https://pubmed.ncbi.nlm.nih.gov/16938407/)

Anecdotal report on benzo taper (one of the comments)

I'm using [agmatine] to get through a benzodiazipine taper I used it the last 5 days amazing relief! I was shocked!

Valerian root extract might help as an alternative to benzos, since it blocks the enzyme that breaks down GABA, enhances GABA receptors in a different way to benzos and increases adenosine (calming).

Further, extracts from valerian root facilitated the inhibition of GABA transaminase activity, the enzyme responsible for breaking down GABA, also measured by an in vitro enzyme assay.
...
It appears that valerenic acid interacts with GABA-A neurons similarly to action of the benzodiazepines, by binding to specific subunits on the GABA-A receptor complex.
...
Neither the γ subunit, which is usually stimulated by the benzodiazepines, nor the α subunits were stimulated by valerenic acid.
...
While valerian acts mainly through GABA interactions its effects may be further mediated by its ability to enhance the effects of adenosine.
...
They found that valerian bound with high affinity to A1 adenosine receptors – with 15-fold greater potency than A2A receptors – competitively displacing [3H]N6-cyclohexyladenosine in a dose-dependent pattern.

These mechanisms likely account for the sedative effects of valerian. Benzodiazepines...additionally act by blocking the reuptake of adenosine and permitting its accumulation.

https://www.sciencedirect.com/science/article/abs/pii/S0944711309002906

Inhibition of NMDA receptors by agmatine is followed by GABA/glutamate balance in benzodiazepine withdrawal syndrome
The present study reveals the possible mechanism of action of agmatine on NMDA receptor at GABA interneurons and glutamate post synaptic neuron that may lead to GABA/glutamate balance during withdrawal syndrome.

https://bjbas.springeropen.com/articles/10.1186/s43088-021-00125-8

 

[50shadesofDave]

Thank you for gifting me those studies, I've read parts and will read further later this evening.
That sounds very promising.

I really appreciate that you've added that to my armoury, I'm really not looking forward to starting a taper, I can't yet anyway due to work commitments, also need a sensible and reliable stock.

Thanks again, and anyone dealing with benzos take care, there is all sorts of shit out there.

 

[Allylbenzene]

.

 

[Allylbenzene]

Regarding endogenous tetrahydropapaveroline (THP) acting as a precursor for morphine in humans. THP forms from dopamine condensing with it's immediate aldehyde metabolite (dopaldehyde). Anything which sufficiently occupies/inhibits the main aldehyde metabolising enzymes (eg ALDH) would lead to dopaldehyde accumulation and increased THP formation.

Urinary excretion of morphine and biosynthetic precursors in mice

It has been firmly established that humans excrete a small but steady amount of the isoquinoline alkaloid morphine in their urine. It is unclear whether it is of dietary or endogenous origin. There is no doubt that a simple isoquinoline alkaloid, tetrahydropapaveroline (THP), is found in human and rodent brain as well as in human urine. This suggests a potential biogenetic relationship between both alkaloids. Unlabeled THP or [1,3,4-D(3)]-THP was injected intraperitoneally into mice and the urine was analyzed. This potential precursor was extensively metabolized (96%). Among the metabolites found was the phenol-coupled product salutaridine, the known morphine precursor in the opium poppy plant. Synthetic [7D]-salutaridinol, the biosynthetic reduction product of salutaridine, injected intraperitoneally into live animals led to the formation of [7D]-thebaine, which was excreted in urine. [N-CD(3)]-thebaine was also administered and yielded [N-CD(3)]-morphine and the congeners [N-CD(3)]-codeine and [N-CD(3)]-oripavine in urine.

These results show for the first time that live animals have the biosynthetic capability to convert a normal constituent of rodents, THP, to morphine. Morphine and its precursors are normally not found in tissues or organs, presumably due to metabolic breakdown. Hence, only that portion of the isoquinoline alkaloids excreted in urine unmetabolized can be detected. Analysis of urine by high resolution-mass spectrometry proved to be a powerful method for tracking endogenous morphine and its biosynthetic precursors.

https://pubmed.ncbi.nlm.nih.gov/20421505/

Parkinson’s disease, L-DOPA, and endogenous morphine: A revisit

It is twenty years since the publication of a clinical report indicating an approximate 20 fold enrichment of morphine, codeine, and the benzylisoquinoline (BIQ) alkaloid tetrahydropapaveroline (THP, norlaudanosoline) in the urine of Parkinson’s disease patients receiving L-DOPA replacement therapy, as compared to naive healthy controls...

These collected results provide putative evidence that endogenous morphine and codeine are synthesized in vivo utilizing L-DOPA and/or DA via the well characterized Pictet-Spengler condensation product THP [40–42] as an early intermediate precursor molecule. A later report demonstrated stereoselective expression of the (S) enantiomer of THP in human brain, thereby providing additional support for a regulated pathway of de novo synthesis of endogenous morphine via enzymatic O- and N-methyl transferase conversion of (S)-THP to (R)-reticuline.

https://pmc.ncbi.nlm.nih.gov/articles/PMC3560700/

We have identified morphine and codeine in human urine by means of gas chromatography/mass spectrometry. Gas chromatography/mass spectrometry was also used to quantitate the two alkaloids and tetrahydropapaveroline (THP) in urine of both normal subjects and parkinsonian subjects receiving L-dopa therapy.

The results indicate that morphine and codeine are synthesized in the body from L-dopa and/or dopamine, via the THP-related pathway.

https://doi.org/10.1016/S0022-3565(25)11471-7

A very old paper from 1990 which articulates my rationale for alcohol mediated aldehyde dehydrogenase inhibition.

Tetrahydropapaveroline is an alkaloid derivative of dopamine. Alcohol, by way of its primary metabolite, acetaldehyde, competitively inhibits nicotinamide-adenine dinucleotide-linked aldehyde dehydrogenase and augments the formation of tetrahydropapaveroline in vitro. The limited capacity of brain to oxidize aldehydes may be of pharmacological importance because it facilitates the production of tetrahydropapaveroline in the presence of drugs which inhibit this enzyme.

https://www.science.org/doi/10.1126/science.167.3920.1005

 

[4DQSAR]

Again - this topic has hoplessly drifted. I hope the mods will fix it soon.

 

[higherconciousness]

So about that ethylbromazolam…
I have a g coming right now. I tried some 6mg bars but was using other benzos as well so it was hard to discern what was doing what. I believe there was a day I used just the 6mg E-bromo bars. I took 12mg and i definitely felt it. Was hardly sedating, but the anxiolytic effects were prominent. Looking forward to diving in deeper with this one. Also nabbed a gram of MD-Pihp. I’m just concerned that this benzo won’t help knock me out. If I’m up one night doing MD, the chances for psychosis are exponentially higher.

 

[Ds]

Hey, can someone let me know what the dose range is on Ethylbromazolam?
Thanks

 

[DepressMyCNS]

I might have to snipe a gram of this shit then.

Test via HNMR Mass spectrometry and rat tests. For posterity

I might have to snipe a gram of this shit then.

Test via HNMR Mass spectrometry and rat tests. For posterity XD

Totally not for personal reaseaexh lol (it's gas imo)

 

[DepressMyCNS]

My thoughts after a couple trials is that this feels like a slightly less potent bromazolam. Have read exaggerated reports of no sedation, short duration, drastically less potent, etc... idk, YMMV, but 1mg of ethylbromazolam is still far more sedating 0.25-0.75mg phenazolam. Of course there is much more impairment/ loss of executive function from 0.75mg phenazolam, but in a blind test I would be guessing.

Getting some soon, dosing suggestions?