Stimulants of the Future

[Refluxer]

Cheers for the link to the paper. I think that was the one I was asking about some time ago. My guinea pigs are starting to drool.

 

[kidamnesiac]

That paper is hilarious
"Dozens of rats were decapitated so that thousands can be saved in the future because it turns out you can use the whole brain..."
those rats are heroes
"...and now we're going to talk about our theories on other peoples work because our data is boring and essentially unhelpful."
What I really like is that they do their experiments at 25 instead of 37, because it is easier to model (diffusion is a normal and perhaps very INTERESTING part of living organisms you lazy pre-personal-computer-linear-line-loving-surrender-monkeys!)

There is a really interesting looking short book in the references section by Maxwell et.al
structural requirements for inhibition of noradrenaline utake by phenetylamine derivatives... in "the mechanisms of nueronal and extraneuronal transport of catecholamines"

too bad its a book

 

[fastandbulbous]

Thiophenmetrazine sounds promising as does alpha,alpha-diphenyl-alpha-(3-thiomorpholinyl)methanol - detailed in the following paper:-

The Synthesis of (A), (+) and (-) a-(3-Thiamorpholiny1)-benzhydrol, a New Selective Stimulant of the Central Nervous System. B. BELLEAU Journal of Medicinal and Pharmaceutical Chemistry (1960)VOL. 2, No. 5 p553.

The paper outlines the additional benefits of using thiomorpholine because of possible metabolic activity about the sulphur atom.

Very interesting F&B. The trouble is it's not possible to tell just by reading those papers what the effects are likely to be like in human subjects

True, but the same could be said of drugs such as 4-MAR and MDPV before they became widely used compounds (& why you dig out as much toxicology relating to primates as possible)

 

[Aidan of TCC]

A link to the paper here

What, I don't get credit for finding it?

 

[Reminisant B]

Thiophenmetrazine sounds promising as does alpha,alpha-diphenyl-alpha-(3-thiomorpholinyl)methanol - detailed in the following paper:-

The Synthesis of (A), (+) and (-) a-(3-Thiamorpholiny1)-benzhydrol, a New Selective Stimulant of the Central Nervous System. B. BELLEAU Journal of Medicinal and Pharmaceutical Chemistry (1960)VOL. 2, No. 5 p553.

The paper outlines the additional benefits of using thiomorpholine because of possible metabolic activity about the sulphur atom.

Wow those are some interesting compounds... I would imagine they are quite hard to synth.

Thio compounds looks very promising in terms of new territory

What about the Benzothiophane analogue of MDMA (like benzofuran but with S instead of O) ? From trying to remember from PIHKAL isn't the MDMA thio analogue not possible or extremely hard. But the benzothiophane compound looks like its available.

 

[haribo1]

I still say go with what we know. The compound on the right is described as being 'active at sub-milligram levels' which seems like it might be good. Possibly the thioalcohol version would elicit some joy, who knows? Has any work on thioephedrine been carried out?

 

[Jamshyd]

Is it just me, or do these compounds (especially Sch-5472) bear similarity to Lefetamine?

 

[haribo1]

J- now your just getting obsessed with SPA, man! If the N in pipradrol was 1 carbon further round the ring & methylated, then it would follow the morphine rule, so that's a possible. Remember,

1-Aromatic system
2-Quaternary carbon
3-2 carbon chain
4-tertiary amine

 

[Reminisant B]

Does anyone know if other analogues of modafinil have been made and tested? (other than adrafinil + the pure isomer armodafinil)

I understand many new pharmaceuticals may target the same receptors but I don't mean the question in that sense.

I mean actual analogues of modafinil - like it could get interesting if something is substituted on the Nitrogen atom.

 

[Reminisant B]

Hmm shame this compound has no literature but looks interesting, almost like a modafinil antagonist.

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=11960525

 

[Reminisant B]

Benzylpiperazine-Modafinil

What about the possibility of Connecting benzylpiperazine to modafinil. (Possible having those two as metabolites but also having new interesting effects)

 

[fastandbulbous]

^ Doesn't always work like that. You'd think that putting an alphamethylphenethyl group on a tryptamine nucleus (nitrogen of side chain)would give a speedy hallucinogen, but you get an inactive compound. The important thing is finding the receptor for a drug, then characterising it and determining the pharmacophore (ideal spacing of main functional groups)

 

[mad_scientist]

Read this paper re modafinil, very interesting...

Jia Zhou, Rong He, Kenneth M. Johnson,
Yanping Ye, and Alan P. Kozikowski

Piperidine-Based Nocaine/Modafinil
Hybrid Ligands as Highly Potent
Monoamine Transporter Inhibitors:
Efficient Drug Discovery by Rational
Lead Hybridization

Journal of Medicinal Chemistry 47(24): 5821-5824

Look at compound "16e" particularly, nanomolar inhibition of dopamine, serotonin and noradrenaline reuptake in a single molecule.

Probably best not posting the full paper on here cos of copyright infringement, site rules ban on posting synthetic routes etc, but heres the structure of 16e, synthesis is 7 steps from arecoline...

 

[Reminisant B]

^ditto, looks really interesting, any chane you could pm it?

 

[Smyth]

It's really the sort of thing that is going to stay confined to the research laboratory. Still, I could say the same about Paxil (which was/is also made from arecoline), and this has been successfully commercialized. Add to this that there are now totally synthetic routes to Paxil which apparently cut down on the cost of manufacture, and its not impossible that financial gains could be made on these novel hybrid compounds provided that they are powered by the major drug companies.

Although not advanced discussion as such, I read and have heard from people who have tried modafinil, that it is really a bit like executive caffeine in terms of its effects. I would find it useful if people can fill me in on this compound as it is still somewhat obscure and it seems like it is gaining in popularity.

 

[mad_scientist]

I've tried adrafinil a bunch of times, back when it was unrestricted (its prescription medicine now because of its supposed abuse potential 8) )

Adrafinil is a prodrug of modafinil so basically very similar effects id imagine, its a useful stimulant for work or study but not euphoric or abusable in any way.

I found it good for drinking alcohol socially as it stops you getting drunk...see personally i don't really like getting drunk but its very socially awkward to just drink orange juice or something when you have to socialise with a bunch of non-drug users who drink heavily at work functions etc, so drop 1200mg of adrafinil before you go out and you can drink for hours with everyone else but it hardly affects you...

 

[Refluxer]

Adrafinil doesn't affect me very much, it makes me a bit more alert and makes it easier to focus for a while. But it doesn't keep me awake at all, like claimed for modafinil. Also, I've developed allergic reaction to it, and get red rashes all over whenever I take it. So I stay away from it nowadays.

 

[nuke]

Although not advanced discussion as such, I read and have heard from people who have tried modafinil, that it is really a bit like executive caffeine in terms of its effects. I would find it useful if people can fill me in on this compound as it is still somewhat obscure and it seems like it is gaining in popularity.

a lot of people on the imminst.org forums use it as a nootropic, there's a ton of praise and dedicated modafinilists there.

 

[Smyth]

^Thanks for that link. Another drug that interests me is selegiline but it seems as though the drug rasagiline is even more potent. In terms of somebody who actually considers 'abusable' or 'rushy' drugs desirable and is not just looking for a 'study aid', which do u think is better out of modafinil and l-deprenyl?

 

[Xorkoth]

I'm prescribed modafinil because it was suspected that I have narcolepsy (although I'm quite sure by now that it was years of excessive lack of sleep). It's useful occasionally, but it's not very effective for me. Caffeine keeps me up more effectively usually. Occasionally 200mg of it will keep me wide awake, but usually it seems to have no effect or very little effect on my ability to stay awake and/or feel awake.