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GHB analogue.

M

markosheehan

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Joined
Sep 17, 2016
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238
Does anyone know of a GHB analogue that acts as a partial agonist towards GABAB receptors but has no affinity to GHB receptors?
 
thats a full agonist. GHB is a partial. I remember reading about one a couple years back I just can not remember. They are out there though.

partial agonists come with less adverse affects like tollerance. so a partial is more desirable.
 
markosheehan said:
thats a full agonist. GHB is a partial. I remember reading about one a couple years back I just can not remember. They are out there though.

partial agonists come with less adverse affects like tollerance. so a partial is more desirable.
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Buprenorphine is a partial opioid agonist, and it creates a significant degree of tolerance; most of the serotonergic psychedelics are only partial agonists, and people build up tolerance at such a rapid rate that re-dosing is usually considered a waste.

The main benefit of a partial agonist is usually that there is a certain ceiling effect, limiting toxicity to some extent.

Basically, if it's recreational, it's going to have tolerance issues.
 
There's GHV, GABOB, etc etc. There's been a couple but those are the main ones I can think of off the top of my head.
 
Help?!?! said:
There's GHV, GABOB, etc etc. There's been a couple but those are the main ones I can think of off the top of my head.
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Isn't GVL/GHV still an agonist at the GHB receptor? It might also be pretty toxic on your organs, given the toxicity of pentanol.

OP is looking for GABA-B partial agonists without GHB receptor affinity, presumably to provide GHB-like benefits without the development of tolerance.

But as I said, they might as well use baclofen - tolerance development still happens with partial agonists. The longer a receptor stays in the active conformation, the more likely it is to be internalized and destroyed, so it matters little whether you achieve that via a high-affinity partial agonist or a low-affinity full agonist (yeah, there may be different effector pathways and such, but that is not necessarily related to a compound's efficacy as an agonist).
 
Oh yeah your right. Read the thread once but say it again and forgot about that. Though GABOB has no affinity at GHB receptor sites as far as I know. It fits the bill in one customer at least. Its true though. Whether its a partial agonist or not it'll cause tolerance all the same.
 
Its not just partial agonists seem to come with less tolerance, they are also just generally safer. sure look at cannabis and synthetic versions. the synthetic versions cause havoc in your body and brain relative to cannabis.

The r isomer of GABOB is interesting,thanks
 
It would be nice to find others related to GHBs structure though as it safety profile could be closer to GHBs rather than a random new chemical.
 
GHB itself or its analogs never seemed to develop much tolerance for me, even when used multiple times a day. Then again I keep doses low.
 
sekio said:
GHB itself or its analogs never seemed to develop much tolerance for me, even when used multiple times a day. Then again I keep doses low.
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Same for the most part. GBL caused tolerance but 3gs of GHB was the same whether I already took a few grams early in different doses throughout the day.

Mark do you have proof to the synth noids? The highly potent ones seem to cause issues but the JWH series seemed to cause little problems. Besides AB-Fubinaca(my personal favorite) and WIN-55-9,212(another favorite)are the only two available actually tested on humans by pharma companies.
 
sorry help, I do not know much about that but if you make a thread here about it you will get good answers
 
markosheehan said:
sorry help, I do not know much about that but if you make a thread here about it you will get good answers
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Users have no real information. You think everything you feel on a drug is real. These are high potency cannabinoids. Could be pretty psychedelic where many people think they feel something. Yeah the high high potency ones cause a lot of trouble just like high potency opioids. Not saying anything bad happened but used moderately or not insanely at least not that many bad things did happen to me or other posters. You can't expect something to happen if you smoke a ton of super potent compound IMO. I just tried to keep it all in check and thankfully it was pretty benign for me.
 
I've read a couple of HOCPCA (3-hydroxycyclopent-1-enecarboxylic acid) in Japan. Well, the vendor sold it in solution of the potassium salt. Faster onset, shorter duration. Lots of ataxia, loss of fine muscle control and heavy sedation. If it wasn't so much of a pain to make in bulk. it would be a winner. I have often wondered if, like triazolam & alprazolam, can the RCs with the triazole ring form the hydrobromo salt. I appreciate bromism is a recognized medical condition BUT given the mass of material, the doses will be low BUT it might be a benzodiazepine-sparing compound medication. Xanax is TID so it would accumulate but the steady-state plasma levels might be at the low end of the therapeutic window. Barbiturates are another potential areal. Phenobarbitone has a long, long, long T? so again it might reach into the window....

I have just realized that we didn't test pyeyzolam for GHB dependence.
 
markosheehan said:
Its not just partial agonists seem to come with less tolerance, they are also just generally safer. sure look at cannabis and synthetic versions. the synthetic versions cause havoc in your body and brain relative to cannabis.

The r isomer of GABOB is interesting,thanks
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Synthetic cannabinoid-related organotoxicity may be more a result of their toxic metabolites (not to mention various impurities/synthesis byproducts) rather than the overaction of cannabinoid receptors. Many of these compounds contain, for example, naphthyl groups, which is not something you want to force on your liver on a daily basis. The effects on the central and peripheral nervous system I would indeed mostly ascribe to the full agonism, though.

With THC, you'll soon encounter a point of diminishing returns where you'll need to exponentionally increase your dose to intensify the high any further. A full-agonist CB1/CB2 agonist, on the other hand, can breeze through that point, and stimulate those receptors to a degree where you'll risk seizures and psychosis when you're using, and very unpleasant withdrawal symptoms when you're coming off them.

However, in the end it still comes down to what dose you're using them at. Buprenorphine is a partial agonist, but it isn't really considered "safer" or "less addictive/recreational" than codeine, even though the latter serves as a prodrug to a full agonist; you can get higher off of half a 2mg suboxone strip (i.e. far less than the ceiling dose) than a dozen 30mg codeine pills.

Baclofen generally has relatively little recreational potential so there are relatively few cases of baclofen abuse, very much in contrast to buprenorphine. Thus I'd assume there isn't too much commercial interest in a selective GABA-B partial agonist. What would be more interesting, IMO, would be a GABA-B agonist that is a mild partial agonist at the GHB receptor, providing a safer alternative to Xyrem for people suffering from narcolepsy, as well as a new treatment option for chronic insomnia or maybe even anxiety disorders.
 
Hodor said:
However, in the end it still comes down to what dose you're using them at. Buprenorphine is a partial agonist, but it isn't really considered "safer" or "less addictive/recreational" than codeine, even though the latter serves as a prodrug to a full agonist; you can get higher off of half a 2mg suboxone strip (i.e. far less than the ceiling dose) than a dozen 30mg codeine pills.
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Well, without tolerance to opioids then sure, you can get much higher off 1mg of buprenorphine than say 200mg of codeine. But if you were dependent on heroin or morphine and needed a weaker opioid just to stave off withdrawals, high-dose codeine would be a much better choice than buprenorphine. Both buprenorphine and codeine have a ceiling effect for two different reasons, buprenorphine is a partial agonist and codeine is a prodrug which also happens to be an inhibitor of the enzyme which turns it into morphine, the conversion to morphine is thus very low, so with higher doses of codeine histaminergic side effects become a problem as well. If you take codeine with CYP2D6 inducer like glutethimide, apparently it becomes a very strong opioid, due to much higher dose conversion to morphine. So what limits codeine recreational/addictive but also painkilling potential is low and limited conversion to morphine, buprenorphine on the other hand is the active drug itself and the role of metabolites is negligible. Thus this comparison can't really reflect the relationship between a full and partial agonist opioid. A more reliable comparison with respect to safety would be to take morphine vs. buprenorphine, but still, the intrinsic activity alone cannot be the factor determining the relative toxicity. For an opioid-tolerant person buprenorphine is certainly much harder to overdose on fatally than morphine, but for opioid-naive person overdose on buprenorphine may be more dangerous due to very high affinity of buprenorphine and naloxone not being strong enough of an antagonist to reverse the effects of buprenorphine.
 
Clubcard, HOCPCA has incredible affinity for the GHB receptor. Do you know any GHB analogue with no affinity to the GHB receptor but acts as a partial agonist to GABA b receptors.?
 
markosheehan said:
Clubcard, HOCPCA has incredible affinity for the GHB receptor. Do you know any GHB analogue with no affinity to the GHB receptor but acts as a partial agonist to GABA b receptors.?
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(2,6-Di-tert.-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930)
N,N'-Dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine (GS39783)

These are positive allosteric modulators of the GABA b receptor. Space-filling & EWG are present in the same relative positions and are derived from propofol. 4-iodopropofol is a less selective but similar PAM researched 20 years ago. The quaternary carbon on the former is to engender conformal isomerism but that is the area that HTS (high-throughput screening) has been used. As to the differences, patents ensure the best medicines are never made. Clearly the latter compound was developed after the former and the team had to avoid patent infringement. The former with the thioether replacing the 2-methyl-2-sec-butanol would be my first port of call but only AFTER I have read every article and even then animal studies. You can have cheap and you can have safe - you can't have both.

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