Glutethimide analogs

[haribo1]

I am interested not in the sedative/hypnotic action of glutethimide, but rather it's ability to make to body produce more CYP2D6 enzymes, thus elevating the level of de-etherified prodrugs.
I have yet to find ANY SAR data for thus class of compound. The only similar compounds (methylprylon & pyrithyldione) apparently don't share this interesting effect.
If the barbiturate 5,5 disubstitution is anything to go by, then 5-(1-methylbutyl)-5-prop-2-enyl- is the most potent (as in Seconal).

The T1/2 is stated as 10-12 hours, so a little too long one would conclude. If my history neuron is working, I seem to remember that the first barb marketed was the 5,5 diethyl derivative which was of low potency. Glutethimide mirrors phenobarbital (and phenobarbitone has a T1/2 of 53 to 115 hours!)

Anyone got further information on this one?

PS I certainly don't want to be messing around with something as plain downright dangerous as barbs. Something that had little or no sedative/hypnotic action but sorted out the codeine/tramadol/oxycodone/hydrocodone/DHC and so on could be quite interesting...

 

[fastandbulbous]

Glutethimide derivatives have some horrible effects on the endocrine system, so they're every bit as dodgy as barbiturates IMO

 

[haribo1]

Oh, I'm not trying to make it out as some kind of wonder-high, but if the analogs follow the barbiturate SAR, then diethyl should be virtually inactive as a sedative/hypnotic but if it retains the OTHER effect...

 

[haribo1]

Does anyone have the patewnt number of the stuff coz I cannot find it...?

 

[muie]

Any Products?

bump please!

Enough time has passed since the start of this thread, during which many chemicals have appeared on the market. I am sure someone is aware of a couple products! Of the top of my head I seem to recall one that is related, though it is used for bodybuilding or even a growth hormone so that is already significantly more dangerous than a simple sleeping aid as was the case with Doriden. On the bright side, most people like myself aren't interested in a full dose experience but rather a small dose enough to create the enzymatic conversions responsible for converting more codeine to morphine.

To the O.P. barbiturates do not work in the same way when it comes to potentiating pro-drugs! Codeine for example was long thought to increase the conversion percentage to morphine by addition of a barbiturate as you suggested! I want to tell you that this is not the case! I have tried it with both phenobarbital & amo-barbital, basically the same effects produced by the former are produced by the latter with the exception of the latter creating a much quicker duration of action. The very same enzymes affected by barbiturates are also affected by the herb St. John's Wort though to a lesser extent and most often with dosage accumulation after 1+ weeks!

On the issue of codeine, it does not help convert more to morphine rather it helps convert more norcodeine, and other non-active metabolites! Since CYP2D6 is the main pathway, taking a barbiturate which inhibits the CYP2D6 won't get you more morphine since the codeine is competing with another drug, (in this case the barbie) for the metabolic pathway! Please look carefully and study best you can how Doriden worked!! It had a very distinct method of converting more codeine to morphine, extremely different from the way *any* barbiturate works, or any other substances that I've encountered.

To put to rest once and for all, the theory that (more) codeine is metabolized to morphine in the presence of a CYP2D6 inhibitor, I have copied and pasted from Wikipedia a paragraph illustrating how inhibition of CYP2D6 actually reduces the amount of codeine converted to morphine.

"Escitalopram, similarly to other SSRIs (with the exception of fluvoxamine), inhibits CYP2D6 and hence may increase plasma levels of a number of CYP2D6 substrates such as aripiprazole, risperidone, tramadol, codeine, etc. As much of the effect of codeine is attributable to its conversion, 10% to morphine its effectiveness will be reduced by this inhibition, not enhanced. As escitalopram is only a weak inhibitor of CYP2D6, analgesia from tramadol may not be affected."

In the methadone maintenance booklet it clearly says to avoid both phenobarbital and St. John's Wort! I've taken 100mg phenobarbital with my normal dose of methadone, along with a good dose of benzos and felt absolutely nothing since the phenobarbital had cancelled out the methadone! Suboxone however works the exact opposite as methadone whereby St. Johns Wort & barbiturates would work to create more of the active metabolite, sometimes to the point of overdose. If someone on methadone maintenance decides to take benzodiazepines with his dose they will feel more sedated however if they take even a strong dose, say 100mg amobarbital concurrently, it will 100% guarantee to cancel the effects of methadone and the person will feel 'sick' as if only having taken a portion of the total dose! As the day progresses one may even feel withdraw starting to set a lot quicker. This comes directly from 1st hand personal experience as well as 2nd hand experiences, as far as methadone goes! Morphine also doesn't work to the full potential in the presence of barbiturates making me really wonder why Fioricets contain both codeine + butabital, instead of 1 or the other!

 

[J.Del]

Yes Doriden (Glutethimide) and Codeine combination was very big in my area of NJ. They were known on the street as "hits" or "Cibas and Codeine" because at one time Ciba manufactured Doriden and the tablet was stamped CIBA on it. Anyway, the Doriden induced a liver enzyme that made the body convert more of the Codeine into morphine,instead of the usual ten percent it made it into eighty to ninety percent and add the sedative hypnotic effect of the Doriden and you got a intensely euphoric long lasting, blissful high, kind of like a mystical experience. Nothing can compare to the Doriden and Codeine high, nothing. Sadly in '93 the government strong armed the pharmaceutical companies to stop manufacturing Doriden, because of the abuse and also because it was obsolete, replaced by the much safer benzo sedative hypnotics like Restoril, Dalmane, etc.. At the time I was doing a four on four which was four Doriden and four codeine tablets, they went for twenty dollars a pop so a four on four cost eighty dollars, money well spent in my opinion. The euphoria, the warmth, the feeling of being "loved"and the feeling of well-being. Nothing even comes close to my beloved Doriden and Codeine. So in '93 when they were discontinued every one started using H , including myself, which pales by comparison. Finding some Doriden would be like finding the holy Grail. I still dream about them. I am on methadone maintenance about twenty years now.

 

[J.Del]

I heard that they were still being made in Hungary, Romania and Bulgaria until 2006. I should have took a trip over there. Like I said, nothing can even come close to the Doriden and Codeine high, nothing.

 

[Limpet_Chicken]

BTW 5,5-diethylbarbiturate is not inactive. Its pretty good actually. At least as long as you don't let the massive half life allow the stuff to build up in your system until it has you by the nackers. I loved veronal. Definitely prefer barb site GABAa ligands to benzo site ones, the main non-barbiturate (by analogy with the 'nonbenzodiazepines'. would be chlormethiazole, strong, pleasant stuff but it doesn't have the AMPA receptor blocking effects of barbs. This is both a pro and a con in various measures.