Article says he has 13 molecules. Probably playing around with different effects.
Certainly partial agonist is what I've heard him bang on about. Alcohol is definitely not a partial agonist
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Professor Nutt's magic jizz (Sentia)
- Thread starter StoneHappyMonday
- Start date
Certainly partial agonist is what I've heard him bang on about. Alcohol is definitely not a partial agonist
AlsoTapered
Bluelighter
Article says he has 13 molecules. Probably playing around with different effects.
Certainly partial agonist is what I've heard him bang on about. Alcohol is definitely not a partial agonist
Nutt isn't a medicinal chemist which is why he mistakenly thought that pagoclone would make a suitable alcohol substitute. But it turned out that the dependence liability was no different to that of conventional benzodiazepines.
Be it a full or partial agonist, it's STILL increasing the flow of those chloride ions.
The truth is, we were able to demonstrate that it was alcohols a1 activity that mediated it's 'addiction' liability because it disinhibits dopaminergenic neurons.
Lateral septum stimulation disinhibits dopaminergic neurons in the antero-ventral region of the ventral tegmental area: Role of GABA-A alpha 1 receptors - PubMed
The mechanisms commanding the activity of dopaminergic neurons of the ventral tegmental area (VTA) and the location of these neurons are relevant for the coding and expression of motivated behavior associated to reward-related signals. Anatomical evidence shows that several brain regions...
pubmed.ncbi.nlm.nih.gov
So things like pyeyzolam don't produce the re-enforcing effects of alcohol. BUT for most people the toxicity of alcohol acts to counter the re-enforcement (from puking to falling over to blackouts to hangovers). But when you remove all of that, it's much more likely that people would choose it to self-medicate anxiety and depression.
In short - pyeyzolam/pyeybazam mixtures or the new compound are clearly a vastly better choice than alcohol BUT they still produce physical dependence. The brain simply adjusts to that increase in chloride ions. Any sane government would enforce a huge tax on alcohol and a much lower tax on the alcohol alternatives... but IF something goes badly wrong when such drugs reach 'stage IV trials' i.e. pharmacovigilance (i.e. reading reports on adverse events caused by a drug that has already obtained a marketing licence), it would be a political disaster.
The funny thing is that the structure of pyeyzolam isn't a secret and any of those Chinese companies making pyrazolam for the RC market could produce it. I think a LOT of people would pay £10 for a pill that got them as drunk as they would from drinking 2 bottles of wine. In short, GABA Labs cannot charge a premium unless their product is significantly better...
And I see NO patents. I suspect the idea of '13 compounds' is disingenuous. It's not 13 NOVEL compounds.
BTW we even worked out that any alcohol-mimic, if consumed with alcohol would potentially result in dangerous CNS depressant effects. So we discovered that the active compound in 'tipplersbane' mushrooms is 1-aminocyclopropan-1-ol. If you add that to an alcohol alternative and someone consumes alcohol, they puke their guts out. It tastes kind of grim so we then had to work out a way of producing a tasteless prodrug. That's how far we got - we were foreseeing risks and mitigating them.
But UK law changed so the amount of funding needed to continue was vast and unlike GABA Labs, we didn't have ANYONE who was prepared to become a spokesperson. Nutt taught me an important lesson. There are people who like to do the work and there are people who like to take the credit - I aim to belong to the former category since their is far less competition.
Really hope the new stuff is kind to the liver.Nutt isn't a medicinal chemist which is why he mistakenly thought that pagoclone would make a suitable alcohol substitute. But it turned out that the dependence liability was no different to that of conventional benzodiazepines.
Be it a full or partial agonist, it's STILL increasing the flow of those chloride ions.
The truth is, we were able to demonstrate that it was alcohols a1 activity that mediated it's 'addiction' liability because it disinhibits dopaminergenic neurons.
Lateral septum stimulation disinhibits dopaminergic neurons in the antero-ventral region of the ventral tegmental area: Role of GABA-A alpha 1 receptors - PubMed
The mechanisms commanding the activity of dopaminergic neurons of the ventral tegmental area (VTA) and the location of these neurons are relevant for the coding and expression of motivated behavior associated to reward-related signals. Anatomical evidence shows that several brain regions...
So things like pyeyzolam don't produce the re-enforcing effects of alcohol. BUT for most people the toxicity of alcohol acts to counter the re-enforcement (from puking to falling over to blackouts to hangovers). But when you remove all of that, it's much more likely that people would choose it to self-medicate anxiety and depression.
In short - pyeyzolam/pyeybazam mixtures or the new compound are clearly a vastly better choice than alcohol BUT they still produce physical dependence. The brain simply adjusts to that increase in chloride ions. Any sane government would enforce a huge tax on alcohol and a much lower tax on the alcohol alternatives... but IF something goes badly wrong when such drugs reach 'stage IV trials' i.e. pharmacovigilance (i.e. reading reports on adverse events caused by a drug that has already obtained a marketing licence), it would be a political disaster.
The funny thing is that the structure of pyeyzolam isn't a secret and any of those Chinese companies making pyrazolam for the RC market could produce it. I think a LOT of people would pay £10 for a pill that got them as drunk as they would from drinking 2 bottles of wine. In short, GABA Labs cannot charge a premium unless their product is significantly better...
And I see NO patents. I suspect the idea of '13 compounds' is disingenuous. It's not 13 NOVEL compounds.
BTW we even worked out that any alcohol-mimic, if consumed with alcohol would potentially result in dangerous CNS depressant effects. So we discovered that the active compound in 'tipplersbane' mushrooms is 1-aminocyclopropan-1-ol. If you add that to an alcohol alternative and someone consumes alcohol, they puke their guts out. It tastes kind of grim so we then had to work out a way of producing a tasteless prodrug. That's how far we got - we were foreseeing risks and mitigating them.
But UK law changed so the amount of funding needed to continue was vast and unlike GABA Labs, we didn't have ANYONE who was prepared to become a spokesperson. Nutt taught me an important lesson. There are people who like to do the work and there are people who like to take the credit - I aim to belong to the former category since their is far less competition.
AlsoTapered
Bluelighter
Oh, ALL of the alternatives are essentially non-toxic.
The ONLY thing that slightly concerns me is that we went with the 7/8 ethynyl moiety to confer selective a5 activity BUT their was some research from the 1990s that showed that the 7/8 trimethyl silyl (-Si(CH3)3) homologues were almost as active.
And while their is no logical reason to fear (organic chemical) drugs that have a silicon in their structure... it's kind of alien. Nobody has ever got far enough with a candidate for it to reach human trials, my intuition is to be suspicious of silanes.
Science | AAAS
www.science.org
Derek Lowe (an esteemed medicinal chemist) has tried compounds with silicon in their structure and to my knowledge toxicity was NEVER an issue and yet it worries me. I have NO logical reason to hold that position but if I'm being honest, if and when a silicon containing drug reaches the market and is shown safe after 30 years... then I will relax. It's purely intuitive on my part but if I used a trimethylsilyl, I think it would worry me.
pharmaceutacomy
Greenlighter
- Joined
- Oct 7, 2023
- Messages
- 1
Gotta say it's a treat to read through your rationale and previous research. I've been ruminating on EtOH substitutes since I first heard of this company years ago and I appreciate the insight and detail.Nutt isn't a medicinal chemist which is why he mistakenly thought that pagoclone would make a suitable alcohol substitute. But it turned out that the dependence liability was no different to that of conventional benzodiazepines.
Be it a full or partial agonist, it's STILL increasing the flow of those chloride ions.
The truth is, we were able to demonstrate that it was alcohols a1 activity that mediated it's 'addiction' liability because it disinhibits dopaminergenic neurons.
Lateral septum stimulation disinhibits dopaminergic neurons in the antero-ventral region of the ventral tegmental area: Role of GABA-A alpha 1 receptors - PubMed
The mechanisms commanding the activity of dopaminergic neurons of the ventral tegmental area (VTA) and the location of these neurons are relevant for the coding and expression of motivated behavior associated to reward-related signals. Anatomical evidence shows that several brain regions...
So things like pyeyzolam don't produce the re-enforcing effects of alcohol. BUT for most people the toxicity of alcohol acts to counter the re-enforcement (from puking to falling over to blackouts to hangovers). But when you remove all of that, it's much more likely that people would choose it to self-medicate anxiety and depression.
In short - pyeyzolam/pyeybazam mixtures or the new compound are clearly a vastly better choice than alcohol BUT they still produce physical dependence. The brain simply adjusts to that increase in chloride ions. Any sane government would enforce a huge tax on alcohol and a much lower tax on the alcohol alternatives... but IF something goes badly wrong when such drugs reach 'stage IV trials' i.e. pharmacovigilance (i.e. reading reports on adverse events caused by a drug that has already obtained a marketing licence), it would be a political disaster.
The funny thing is that the structure of pyeyzolam isn't a secret and any of those Chinese companies making pyrazolam for the RC market could produce it. I think a LOT of people would pay £10 for a pill that got them as drunk as they would from drinking 2 bottles of wine. In short, GABA Labs cannot charge a premium unless their product is significantly better...
And I see NO patents. I suspect the idea of '13 compounds' is disingenuous. It's not 13 NOVEL compounds.
BTW we even worked out that any alcohol-mimic, if consumed with alcohol would potentially result in dangerous CNS depressant effects. So we discovered that the active compound in 'tipplersbane' mushrooms is 1-aminocyclopropan-1-ol. If you add that to an alcohol alternative and someone consumes alcohol, they puke their guts out. It tastes kind of grim so we then had to work out a way of producing a tasteless prodrug. That's how far we got - we were foreseeing risks and mitigating them.
But UK law changed so the amount of funding needed to continue was vast and unlike GABA Labs, we didn't have ANYONE who was prepared to become a spokesperson. Nutt taught me an important lesson. There are people who like to do the work and there are people who like to take the credit - I aim to belong to the former category since their is far less competition.
Couple questions though,
1. Was the point of utilizing 1-aminocyclopropan-1-ol to improve safety in comparison to say, disulfiram? Or was it more related to regulatory processes/market of natural ingredients?
2. How did you go about identifying the receptor subtypes associated with EtOH? Did you publish your findings?
AlsoTapered
Bluelighter
1 - Yes. Because it's natural it's not subject to receiving a marketing licence.
2 - Ethanol's affinity for the various receptor subtypes had already been published, we KNEW that a1 & a5 were the most significant so, we developed selective a5 ligands (the Z-drugs are a1 selective so we didn't need to develop probes),
And the work itself hasn't been published although Alcorette published patents for the compounds we had developed up to that point.
Beyond that, nothing has been published as that awaits patenting. Some aspects are somewhat unique and so unlike the earlier patent, it's significantly more complex to provide legal protections to all aspects. That's why I haven't detailed any of the compounds.
In short, we are happy to allow GABA Labs to have all the publicity knowing that the brewing industry (the obvious people to distribute an alcohol mimic) IS aware of our work.
Tranced
Bluelight Crew
Is the bottle still up for a try @LoginNotSecure?
Haven't read whatevers going on in this thread of late but will gladly smash the rest to see it works or not.
Haven't read whatevers going on in this thread of late but will gladly smash the rest to see it works or not.
Can buy some online.. sentia. Really mild I think
AlsoTapered
Bluelighter
I looked into the (all natural) ingredients of Sentia.
Ingredients:
B1, B12, water,
botanical extracts:
(magnolia bark (magnolia officinalis),
linden flower (tilia cordata),
passionflower (passiflora incarnata),
ashwagandha (withania somnifera),
liquorice (glycyrrhiza glabra),
rose (rosa damascena),
tulsi (ocimum teniflorum),
rhodiola (Rholdiola Rosea),
hawthorn(crataegus monogyna),
damiana (turnera diffusa),
gentian (gentiana lutea),
agave syrup (agave tequilana),
aronia concentrate (aronia melanocarp),
blackberry concentrate (rubus fruticosus),
black carrot concentrate (daucus carota ssp),
glycerine, spice extracts, acids: citric acid, malic acid, preservative: potassium sorbate.
Technically the PSA prohibits the sale of all psychoactives but I presume that a SPECIFIC chemical would have to be identified and I'm guessing that in the above are thousands of chemicals so identifying actives would be next to impossible.
Yes. Everything has been already approved for thousands of years or some similar party line
LoginNotSecure
Bluelighter
@F.U.B.A.R. had it I’m afraid.
LoginNotSecure
Bluelighter
Not Jewish
Tranced
Bluelight Crew
Greedy cunt
So far, all SENTIA variants are entirely plant-based, ie botanicals. However, ‘SENTIA Plus’, to be launched in 2026 in the USA, will be the first-ever beverage available to the consumer public to contain Alcarelle, a synthetic ingredient currently under development by Nutt’s team at GABA Labs
Alcarelle is expected to become available in the USA in 2026 and in EU and Asia-Pacific during 2027/2028.
Latest news
Alcarelle is expected to become available in the USA in 2026 and in EU and Asia-Pacific during 2027/2028.
Latest news
Last edited:
AlsoTapered
Bluelighter
I doubt it. They claim to have patent-pending synthetics... their are NO patents in the name of GABA labs.
If I simply missed their patents I really would like to see them - mostly because they bought 3 designs from me which means they own them (they offered shares instead of cash, I said no) but they did continue to co-respond (I kept all the E-mails) so if they present one of my compounds I DIDN'T sell them, I would like to know.
I sent Professor Nutt the 'supercats' and he replied enclosing my original E-mail so I have the proof. I even timestamped them so they are in a blockchain somewhere.
As it is, It's going to be a pyeyzolam derivative if anything.
If I simply missed their patents I really would like to see them - mostly because they bought 3 designs from me which means they own them (they offered shares instead of cash, I said no) but they did continue to co-respond (I kept all the E-mails) so if they present one of my compounds I DIDN'T sell them, I would like to know.
I sent Professor Nutt the 'supercats' and he replied enclosing my original E-mail so I have the proof. I even timestamped them so they are in a blockchain somewhere.
As it is, It's going to be a pyeyzolam derivative if anything.
You are very clued up on this. I'm afraid I don't know the ins and outs of it.
But it did say he had 13 compounds in a previous article. We only need 1 for the product to be released initially. Ball rolling so to speak.
AlsoTapered
Bluelighter
Yeah - the problem is that a synthetic alcohol replacement is a drug. It's going to be subject to the same safety regime that a candidate medicine would undergo. After all, it's not like a pharmacist will be involved so it would have to be proven safe beyond all doubt.
That kind of testing costs simply HUGE amounts of time and money.
I took the money because I pointed this out and they didn't really have an answer. The EU will require EU testing, the US will require US testing and so on.
Believe me, pyeyzolam IS much safer than ethanol... except if you MIX it with alcohol. Designing something that won't do that... I don't know how you would do it. I did point out that their are some natural compounds that act like disulfiram (Antabuse) but apparently that's essentially allowing a buildup of acetaldehyde in the body and is itself dangerous which is why disulfiram is no longer in use.
I don't think a warning label would cut it - not if it's a potentially fatal interaction.
That kind of testing costs simply HUGE amounts of time and money.
I took the money because I pointed this out and they didn't really have an answer. The EU will require EU testing, the US will require US testing and so on.
Believe me, pyeyzolam IS much safer than ethanol... except if you MIX it with alcohol. Designing something that won't do that... I don't know how you would do it. I did point out that their are some natural compounds that act like disulfiram (Antabuse) but apparently that's essentially allowing a buildup of acetaldehyde in the body and is itself dangerous which is why disulfiram is no longer in use.
I don't think a warning label would cut it - not if it's a potentially fatal interaction.
£15m to crack the US market I read. We wait with baited breath.
