Stimulants Novel RC Stim candidates or no ??

[CarryBagMan]

Hi, could a chemist or pseudo-chemist who knows something about stimulant research chems take a look at these chemical diagrams and be able to tell to some degree if they are 'recreationally viable" or "interesting" or merely flotsam and jetsam? Thank you so much for your help/expertise/educated guesses.

 

[4DQSAR]

Lefetamine is the closest. Take a look at lefetamine and pyrophenidone. Both compounds show that a second benzene ring will act as a bioisostere of an n-propyl moiety. But you can't induce SERT activity in either.

If you want a novel entactogen, (R) 7,α dimethyl tryptamine ((R) 7-methyl AMT) is your boy.

If you have chem office, overly 3-methoxy-4-methyl amphetamine (MMA) with that N of the indole overlaying the O of the methoxy - voila, they overlay PERFECTLY. Of course, I think it hasn't turned up because MDMA is so simple to make from safrole and with China cutting down forests of trees loaded with safrole-containing oils, who knows when if ever it becomes cheaper than MDMA. I guess it's legal almost everywhere, but amazingly most people go with 'cheap but illegal' over 'costly and legal' every time.

 

[Smyth2]

Lefetamine is the closest. Take a look at lefetamine and pyrophenidone. Both compounds show that a second benzene ring will act as a bioisostere of an n-propyl moiety. But you can't induce SERT activity in either.

If you want a novel entactogen, (R) 7,α dimethyl tryptamine ((R) 7-methyl AMT) is your boy.

If you have chem office, overly 3-methoxy-4-methyl amphetamine (MMA) with that N of the indole overlaying the O of the methoxy - voila, they overlay PERFECTLY. Of course, I think it hasn't turned up because MDMA is so simple to make from safrole and with China cutting down forests of trees loaded with safrole-containing oils, who knows when if ever it becomes cheaper than MDMA. I guess it's legal almost everywhere, but amazingly most people go with 'cheap but illegal' over 'costly and legal' every time.

See 7-Methyl-Alpha-Ethyltryptamine [13712-80-6]

7-Methyl-alpha-ethyltryptamine

7-Methyl-alpha-ethyltryptamine | C13H18N2 | CID 57469234 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.

pubchem.ncbi.nlm.nih.gov

Szmuszkovicz Jacob, US3296072 (1967 to Upjohn Co).
Szmuszkovicz Jacob, US3365464 (1968 to Pharmacia and Upjohn Co).

 

[Smyth2]

I checked some of my other tryptamines and found one called:

MP-809
4-Methyl-a-methyl-tryptamine
[3569-29-7]

[1] Some Rationales for the Development of Antidepressant Drugs, JOHN H. BIEL, Chapter 10, 114-139. DOI: 10.1021/ba-1964-0045.ch010
[2] Albert Dr Hofmann & Franz Dr Troxler, CH387634 (1965 to Sandoz AG).
[3] AZIMA H, ARTHURS D, SILVER A, AZIMA FJ. The effect of MP-809 in depressive states: a multi-blind study. Am J Psychiatry. 1962 Dec;119:573-4. doi: 10.1176/ajp.119.6.573. PMID: 13965759.

 

[4DQSAR]

Yeah - as soon as you start substituting indole systems, the chemistry gets kind of 'fun' in a totally not-at-all-fun way.

Now a 4 substitution is partiularly interesting because of course, if you overlay your PEA and your tryptamine, the benzylic carbon OF that PEA is at the 4 position.

Great refs @Smyth2 - very much appreciated.

 

[Conky]

I checked some of my other tryptamines and found one called:

MP-809
4-Methyl-a-methyl-tryptamine
[3569-29-7]

[1] Some Rationales for the Development of Antidepressant Drugs, JOHN H. BIEL, Chapter 10, 114-139. DOI: 10.1021/ba-1964-0045.ch010
[2] Albert Dr Hofmann & Franz Dr Troxler, CH387634 (1965 to Sandoz AG).
[3] AZIMA H, ARTHURS D, SILVER A, AZIMA FJ. The effect of MP-809 in depressive states: a multi-blind study. Am J Psychiatry. 1962 Dec;119:573-4. doi: 10.1176/ajp.119.6.573. PMID: 13965759.

Restricted access for [1]

 

[4DQSAR]

Restricted access for [1]

Sci-Hub | Some Rationales for the Development of Antidepressant Drugs. Advances in Chemistry, 114–139 | 10.1021/ba-1964-0045.ch010

 

[Conky]

Sci-Hub | Some Rationales for the Development of Antidepressant Drugs. Advances in Chemistry, 114–139 | 10.1021/ba-1964-0045.ch010

Thank you

Good read so far on page 7 but not sure why there's a paywall for something that contains information originally published in 1964

It seems they thought methylphenidate was a better antidepressive/antifatigue medication compared to amphetamine due to a lack of tolerance build up or post drug depression, among other things.

 

[4DQSAR]

Thank you

Good read so far on page 7 but not sure why there's a paywall for something that contains information originally published in 1964

It seems they thought methylphenidate was a better antidepressive/antifatigue medication compared to amphetamine due to a lack of tolerance build up or post drug depression, among other things.

Not a problem - share the goodness.

I would be VERY cautious in believing what researchers were claiming 60+ years ago. Depression is an extremely difficult mental illness to manage and while I feel sure medication has it's place, in truth, I think person centred councelling (client centred therapy) is actuallly the very best option. The work of Carl Rogers is a cornerstone of how I try to live my own life.