• Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

  • N&PD Moderators: Skorpio | someguyontheinternet

Sedatives of the Future

f&b,

I see your point of view with respect to certain R-Cl's (where R=alkyl) N-alylating properties of inappropriate substrates, but take any quick perusal of the PDR or a Merck Index and you will see that this N-alkylation of DNA/RNA does NOT OCCUR with Ar-Cl compounds (where Ar=aromatic).

For example,
See the structure of sertraline (Zoloft) or trazodone (Deseryl). If it did Geodon (ziprasidone) would not be making the psychiatric blockbuster selling year its been having either.

Furthermore and more on topic,
I have never heard of this phenomenon occurring with chloral hydrate.

N-methyl-3,4-di-chloro-alpha-methyl-phenethylamine hydrochloride, anyone?
 
There is a drug based on muscimol thats in stage 3 trials at the moment. I think it's another GABA thing.
 
Why is there no real mention of tropane derivatives. I know, I know, tropanes are bad at recreational doses, but who is to say there is no perfectly good tropane sedative without all of the side effects of the well known ones( atropine(well atropine is a stimulant, but still), hyoscamine, scopolamine, etc)?? Maybe I am just playing the devils advocate here, but I still beleive there is some promise in this family.
 
Acute Hepatitis Associated with the Chinese Herbal Product Jin Bu Huan

Herbal products are rapidly gaining popularity in North America as remedies for various medical conditions. Jin Bu Huan Anodyne Tablets (Lycopodium serratum), a traditional Chinese herbal remedy, has been used for more than 1000 years as a sedative and analgesic but has only been available in the United States for 10 years [3]. The alkaloid levo-tetrahydropalmatine is responsible for the morphine-like properties of Jin Bu Huan [4].

A recent study [5] described three children who had taken unintentional overdoses of Jin Bu Huan tablets and who developed central nervous system and respiratory depression with bradycardia. We subsequently identified three adult patients with acute hepatitis associated with Jin Bu Huan ingestion and reported this information to the Centers for Disease Control and Prevention and to the Food and Drug Administration [6]. In the present report, we describe the clinical and laboratory features of seven adult patients (including the previously described patients) who ingested Jin Bu Huan and discuss possible mechanisms for Jin Bu Huan hepatotoxicity.
Click to expand...

The hepatotoxicity makes me worried but the compound itself may not have that problem, and the drug is unscheduled pretty much everywhere as far as I know.

Oddly enough:

We have recently studied several natural product constituents which have effects on the CNS. (1) Tetrahydropalmatine (THP) and its analogues were isolated from Corydalis ambigua and various species of Stephania. (+)-THP and (-)-THP possess not only analgesic activity, but also exert sedative-tranquilizing and hypnotic actions. Results of receptor binding assay and their pre- and post-synaptic effects on dopaminergic system indicate that (-)-THP and (-)-stepholidine are dopamine receptor antagonists while (+)-THP is a selective dopamine depletor.
Click to expand...

It also inhibits hyperactivity in rats caused by oxycodone. Maybe useful for speed ODs?

[STUDIES ON THE PHARMACOLOGICAL ACTIONS OF CORYDALIS. VIII. STRUCTURE-ACTIVITY RELATIONSHIP OF ANALOGUES OF CORYDALIS B (TETRAHYDROPALMATINE)]
[Article in Chinese]
KIN KC, TANG XC, HSU B.
Click to expand...

If only it wasn't in chinese..
 
Last edited:
^dopamine receptor antagonists and dopamine depletors are not really fun drugs. Actually, they take all the fun away and make you a zombie. Resembles reserpine. So I don't think that THP and derivatives are the sedatives of the future for Epicureans.
 
Oh, I agree that they might finally have found a totally unfun sedative in THP.
 
I can confirm THP has no recreational potential. Good sleep aid though, and readily available. Some claim it is also a good analgesic.
Methaqualone is not that interesting but is a good way to knock out. Too bad it is so hard to find. I remember an episode of cops where they busted a crack dealer, and he had a bag of grey chunky material that the cops said was quaalude to come down after freebasing... Never could find a reference for street distribution of the stuff.
What would be great would be something with the same effects as seconol. That stuff is a fantastic, but is unavailable. I suppose barbituates would not make good reseach chems due to the low therapeutic index and addiction potential.
GHB and GBL have to be two of the best sedatives, though there so far has been nothing to replace them. Reports of GHV and gammavalerolactone, and gammacrotonolactone all fell short of the original. I tried GHV, and it was a mild sedative with none of GHBs other properties (some reports about the latter when it was around). The literature does not seem to contain a worthwhile and still legal analog of GHB. Phenibut and GABA just do not cut it.. the sad part is that GBL was so cheap when it was legal...there are no other mass-produced industrial chemicals that share this property (not including 1,4BDO which is very inferior and also extinct).
 
How about suriclone? It's a full agonist at "diazepam insensitive sites" on the GABA-A protein, and a group of volunteers rated both 0.4mg suriclone and 1mg xanax to be sedative/helpful on a self-rated well-being checklist.

Linkie
Linkie

Pagoclone's another one, but hasn't gone commercial yet. This one's a partial agonist @ GABA-A, therapeutic at around 1mg, and a bunch of "healthy recreational drug users" say 5mg pagoclone's similar to 30mg diazepam. Apparently since it's a partial agonist it's missing sedative effects.
It's metabolite, 5-hydroxy-pagoclone's got higher affinity for the GABA protein apparently(10-20 fold), and does show sedative effects in mice. Maybe the matabolite's a full agonist.

Linkie
Linkie

These are in the same chemical structure class as zopiclone by the way.
The structures you can find on pubmed.
 
3-alkyl-substituted-GABA, should be alcohol/GHB like in effect, if not that at least sedative, eg 3-ethyl-GABA, 3-propyl-GABA. You can make these easily and the precursors are uncontrolled.
 
Last edited:
yeah, it probably does (which will reduce neurotransmitter release), but it probably binds more effectively to gaba receptors than pregabalin which barely binds at all. It'd probably be more fun than lyrica, but this is all speculation. it's also similar to gabapentin which, however, is even less effective at alpha-2-delta and generally pretty useless. there's also valproic acid..
 
Last edited:
I am amazed such simple analogues of GABA haven't been explored.

Although possible they have and just turned out duds / Highly addictive. (?)

Lyrica to me seems a dirty drug - by that I mean complex with more than one action and lots of side effects.
 
Hey, I bet 3-hydroxyethyl-GABA might be pretty effective, too.

i think the problem lies with the potency and the lack of interests in things with alcohol-esque effects, since there are already so damned many of them.
 
^Very True

Do you mean hydroxy-methyl-gaba ? That would be a GHB molecule with a methyl-amino group added?

Both probably interesting compounds.

I remember reading an article a while ago suggesting a partial benzo agonist as a possible ideal alcohol substitute. (prob not though)
 
It seems the theme of them is to stick a big group (from ethyl to chorophenyl) into the beta carbon position. Well if one large is good, two smaller might be better (those two groups, well ethyl & phenyl - ignore the chlorophenyl group - have a certain history, like the development of the barbiturates). I wonder what a butyl & an ethyl or a sec-pentyl & ethyl would be like? Or their lactones
 
You must log in or register to reply here.
Top