Benzos Ethylbromazolam

[Working_Class]

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

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

 

[4DQSAR]

Do any of these actually prohibit alcohol from
Working if you drank on top of taking it? Similar to bupe more strongly binding the same site morphine dose but not agonizing it anywhere near as much thus preventing one from getting high on the drug of abuse?

No - that is why the original design included a naturally occuring (thus easier to get through certain testing requirements) that produces extremely unpleasent effects if even a small quantity of ethanol is consumed.

The later one also manages this - all in a single molecule.

 

[4DQSAR]

Antabuse (disulfiram) was disregarded on day 1 becuse it has a host of (some severe) side-effects. Again, if someone is necking two bottles of vodka per day, it's appropriate, but if your goal is an alcohol alternative for the masses, you simply cannot accept those problems. It would INSTANTLY be blocked but so would any compound that if consumed with alcohol could cause fatal CNS depresson.

We played out every trick we could think of that the alcohol industry might use to discredit and undermine the development and GSL of an alcohol alternative BY the alcohol industry.

So something from nature reduces issues as does the whole thing being a single compound.

It's not black magic or even very clever. It's more a case of lateral thinking. The goal was always:

1-Safe
2-Legal
3-profitable

1 we have, 2 is down to lawyers, 3 is down to scaling.

But the alcohol industry could just sell the stuff in solution i.e. it uses the infrastructure of the alcohol industry and the licencing laws already in place around the sale and consumption of alcohol.

Also leaves a neat trace metabolite so the police can easily check if someone is under the influence of the stuff without much new technolgy - if you can test ethanol in breathe, you can just as easily test the metabolite.

We did a lot of thinking.

 

[Skorpio]

Met them both.

The science is extremly good and amazingly comprehensive. I wouldn't have mentioned it otherwise.

But they LIKE to be in the limelight all the time. They are both essentially trying to sell their respective research on the basis of their fame. They neglect to mention that in fact it was the work of dozens of people. I don't expect a name-check of teams, but to infer that they are everything seems unfair to their respective teams.

Unfortunately this phenotype is fairly common in scientists who have had a big career. Probably not the majority of them, but a good enough amount to make some meetings with heroes awkward.

 

[4DQSAR]

Unfortunately this phenotype is fairly common in scientists who have had a big career. Probably not the majority of them, but a good enough amount to make some meetings with heroes awkward.

It is mostly limited to scientists who are essentially selling themselves, Some find they enjoy a certain amount of attention.

What's that old saying about fame? It's addictive but not satisfying.

But I do find it interesting that I wouldn't class either of them to be anywhere as good as they think they are. They ARE excellent, but not as good as they seem to believe they are.

The few medicinal chemists I've known that I genuinely consider to have been geniuses share a commonality. Humility - the acceptence that they don't know everything and indeed everything they know could be wrong. Cerrtinly Nutt and Cook are very unhappy to be corrected. They know enough not to simply refuse to accept that there was an error, but they never admit fault. EVER. I wonder if, in their heads, they know that it was a team memer who actually made the error... but then they would have to admit there was in fact a team. If YOU take all the credit, isn't it reaspnable that you equally have to accept all the fault?

 

[Skorpio]

It is mostly limited to scientists who are essentially selling themselves, Some find they enjoy a certain amount of attention.

What's that old saying about fame? It's addictive but not satisfying.

But I do find it interesting that I wouldn't class either of them to be anywhere as good as they think they are. They ARE excellent, but not as good as they seem to believe they are.

The few medicinal chemists I've known that I genuinely consider to have been geniuses share a commonality. Humility - the acceptence that they don't know everything and indeed everything they know could be wrong. Cerrtinly Nutt and Cook are very unhappy to be corrected. They know enough not to simply refuse to accept that there was an error, but they never admit fault. EVER. I wonder if, in their heads, they know that it was a team memer who actually made the error... but then they would have to admit there was in fact a team. If YOU take all the credit, isn't it reaspnable that you equally have to accept fault?

Who would you list as your fave med chemists? I remember way back you shared some cordial remarks here with Dan Lednicer.

Closer to my area, I think Bryan Roth does good work (and his protégés do too), but no idea how the dude carries himself.

 

[Smyth2]

Get-73 has been investigated for the treatment of alcohol dependence.

 

[Smyth2]

^I've seen some encouraging work from a chemist called Amy Hauck Newman over recent years.

Most of my favorite chemists are either dead or retired now though.

 

[4DQSAR]

Who would you list as your fave med chemists? I remember way back you shared some cordial remarks here with Dan Lednicer.

Closer to my area, I think Bryan Roth does good work (and his protégés do too), but no idea how the dude carries himself.

Along with the other medicinal chemists at the Upkohm Drug Discovery laboratory (except Jacob - who Dan never said anyhing bad about, he merely asked if we could talk about something else), I always held Bary Shatpless in high regard as even with a Nobel Prize under his belt, he admits to the fact that the more we learn, the more we don't know. That is rare in my experience. BS is also very clear on laboratory safety which I feel speaks well of him. I've only seen him lecture once but he did say 'Good question - I don't know' which I respected more than someone who would assert it not to be important (a common response) when in truth, you don't KNOW what might be important.

It seems to be a generational thing. The guys who are now in their 80s or older who retain that old school approachable nature. Maybe it's when they retire and can look back and reflect. I honestly don't know.

While there are many medications designed to help dependent alcohol users, in hospitals we still use simple diazepam and clomethiazole for the acute phase of withdrawal. Treating the impuses over months or even years is a totally different issue. Valuable, but differenct.

In our case, we just needed to preculude someone consuming the alcohol mimic and alcohol at the same time. If someone drinks alcohol one day and the alcohol alternative on the next - we need to ensure that our 'additive' WON'T make someone ill. That would be an issue for us,

 

[Smyth2]

I made a wikipedia draft on Fosenazide (Gidifen, Hydifen) if you are interested in exploring alternatives to alcohol.

The GET-73 draft was also accepted recently.

 

[4DQSAR]

RULE 2 - NEVER trust Russian medicines.

An organophosphorous compound with a hydradize - if I didn't know, I would assume it to be a toxin. Hydrazides in particular are fond of forming co-valent (irreversible) binding to sites hence their use in MAOIs.

I suppose in a nation with an average live expecetency in men in the low 50s and where alcohol kills so many, ANYTHING would be accepted as the lesser evil.

But we have clomethiazole and diazepam which have worked for 70 years and continue to be used. I think both are available in Russia so I cannot quite see where this would fit in.

I do know that all manner of random stuff that showed decreased alcohol consumption in animal models has been tried and none of them work. I suspect it might be like antidepressants i.e. why an animal consumes alcohol may not model why people drink. Another class where we stumbled on what is still considered the 'gold standard' 70 years ago and since then it's only the overdose risk of the tricyclics that has driven the development of new agents.

I haven't read the paper but with the SSRIs I DID read every paper and patent and the common factor was that they would compare the highest prescribable dose of the new drug with the very lowest dose of amitryptaline thought to act as an antidepressant and then say the two had 'similar effacacy'. So I've learn that if someone has a new medicine, expect them to design trials to show their drug in the best possible light.

 

[pcplease]

heterocyclics amitriptyline and mirtazepine have always been much more noticeably more affective than SSRIs, from paxil to prozac to vybryyd(?), were.

 

[Smyth2]

If amitriptyline is too weak to be of clinical benefit I found stronger agents, namely Danitracen & one by Parthasarathi Rajagopalan:

 

[4DQSAR]

Well Daniracen went through quite a few studies but wasn't adopted. I DO keep pointing out that as things stand, pharmacutical companies are not required to pubish any trials which is why I support www.alltrials.net

Because nobody who designs a novel medication is EVER going to let anyone read the issues it has. I keep mentioning that we still use amitryptaline as the 'gold standard' but in a deceptive manner.

https://sci-hub.st/10.1021/jm00374a002

As it is, just making something more 'potent' doesn't appear to add value. Yes, the MAJORITY of people will not be prescribed the best antidepressent for them the first time they go to their doctor so there is value in variety.

But who knows what the toxicity is in man? The duration of action? The possibility of it interacting with other medications? All that really dull stuff that any medicine has to go through. It now takes an average of 13 years for a patented medication to get a licence. It costs billions. So raw data can be interesting - but it's a TINY subset of the data required.

If you are battling depression, if nothing licenced in the UK works, it's entirely possible to get licenced antidepressants from other nations. It's not as if they are CDs, Japan seems to use an entirely different set of antidepressants BUT you might want to ask if genetic vaiance might mean an antidepressant of reasonable utility for Japanes people might not work as well for people of European heritage.

But I see absolutely no use case for systematically going through every single antidepressant that ever been patented or even just had a few papers written about it and setting up Wikipedia pages for them all. You have absolutely know way of knowing if they are safe, let alone if they work. I do keep pointing out that animal models of depression remain incredibly limited so choosing based on Ki for a given receptor is absolutely no guied to the utility of such things.

Wikipedia does keep a record and I know from experience that they will just remove stuff if nobody ever reads them.

Anyone in the business of actually developing a novel antidepressant wouldn't touch Wikipedia with a barge pole because absolutely ANYONE can modify a page. I know, I purposefully introduced an entirely fabricated reference into a popular page and it still took over two years for anyyone to even chack if the reference actually existed! It is NOT a reliable source.