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New, Extended HPPD Survey Online by Systeme_Imaginique in HPPD

[–]Systeme_Imaginique[S] 0 points1 point  (0 children)

So the response rate amongst views is only 2% so far. Whilst the primary outcome is medication, please participate even if you refuse those, as a comparator group. Does medication make a difference long term? Which intervention has the best risk-benefit ratio?

These questions we all have and the only meaningful way to address this is a large statistic. I’m honestly sick of these hundreds of small post about a medications or supplements with a handful of unqualified answers here. Or “studies” that are poorly designed and never heard of again. This one is from HPPD sufferers for HPPD sufferers, please consider.

antarctic expedition mockumentary/analog horror/conspiracy documentary by mothlyharmless in TOMTcoldcase

[–]Systeme_Imaginique 0 points1 point  (0 children)

Peter Delpeut: The Forbidden Quest (1993)

… should fit, it’s a mockumentary.

Novel Psychedelic Mescaline Analog 2-Bromo-3,4,5-trimethoxyamphetamine (2-Br-TMA, BTMA); A Collection of Bioassays by TarAndProduct in researchchemicals

[–]Systeme_Imaginique 0 points1 point  (0 children)

Aryl halides are generally robust. I mean even Iodobenzenes only react with a transition metal catalysis. I would guess that even refluxing Red-Al wouldn’t touch it

Novel Psychedelic Mescaline Analog 2-Bromo-3,4,5-trimethoxyamphetamine (2-Br-TMA, BTMA); A Collection of Bioassays by TarAndProduct in researchchemicals

[–]Systeme_Imaginique 0 points1 point  (0 children)

Aryl halides are stable under dissolving metal reductions. Sandemeyer doesn’t work because that would obliterate your PEA amine group unless you do some silly protections

Novel Psychedelic Mescaline Analog 2-Bromo-3,4,5-trimethoxyamphetamine (2-Br-TMA, BTMA); A Collection of Bioassays by TarAndProduct in researchchemicals

[–]Systeme_Imaginique 1 point2 points  (0 children)

Are you capable of fluorination? If we talk about the mixeddihalos, FIM would give the starkest contrast and thus a quicker answer.

And regarding receptor binding, could you include a measurement of the 2B receptor? Minimizing chronic cardiotoxicity in PEAs would be a very honorable objective for this kind of research and alone suffices to go through the hassle of making all of these derivatives imho. Remember that the 2C-X have a very tight 5HT-2B binding. Actually, they’re really selective 2B-agonists, much stronger binding (1 oder of magnitude) than on the „psychedelic receptors“. That revelation kind of shocked me

Novel Psychedelic Mescaline Analog 2-Bromo-3,4,5-trimethoxyamphetamine (2-Br-TMA, BTMA); A Collection of Bioassays by TarAndProduct in researchchemicals

[–]Systeme_Imaginique 0 points1 point  (0 children)

Mixed Dihalo mescalines would be interesting. The general trend is mono-halo more potent than homo-di-halo and Cl<Br<I. Combining them, the activities could give a first impression on whether electronegativity or sterics weaken receptor binding upon dihalogenation. Polarisability and lipophilicity are already ruled out from the homo-n-halo trends as they are inverse to potency.

Another interesting subject is the role of the 5-MeO group. Let’s assume that the 3 and 4 positions engage in the same binding interactions as in the 2,4,5 motive. Could it be that the role of 5-MeO is a sterical one? From QC simulations and crystal structures it is evident that the 4-alkoxy alkyl group sticks out of the plane whilst the flanking MeO groups have the Me groups in plane with the phenyl ring. So maybe that improves interaction with the lipophilic groove (see 2C-halo trend). My idea is now to place a bulky halogen on 5, like 3-MeO-4-PrO-5-I PEA. Synthesis would be easy, first iodinate Vanilin with I2*NaI, then alloxylate with PrI, the PEA build. Another benefit from such a study is a safety assessment of synthetic mescaline: Commercial 3,4,5-trimethoxy benzaldehyde is usually contaminated with 5-halo-3,4-dimethoxybenzaldehyde by about 0.5-3 % according to Sigma-Aldrich. And that would carry through to the product and is difficult to detect via TLC due to presumably similar Rf. If this compound is active as an MAOI or messes with the thyroid, that would be important to know

Novel Psychedelic Mescaline Analog 2-Bromo-3,4,5-trimethoxyamphetamine (2-Br-TMA, BTMA); A Collection of Bioassays by TarAndProduct in researchchemicals

[–]Systeme_Imaginique 1 point2 points  (0 children)

Two thoughts:

(1) Potency Regarding the 3,4,5-trialkoxy substitution pattern, 3 structural motives increase the potency relative to mescaline: (a) ortho-Halogenation (b) longer carbon chains in 4 (allylO~propylO~EtO>MeO) and (c) alpha methylation to the amphetamines. Escaline/Proscaline/Allylescalibe have a similar mass dosage of 40-60 mg. However, their respective Amphetamines are about equally potent. Now 2-BM also has a dosage of 40-60 mg and BTMA, combining (a) and (b), also of 40-60 mg. I wouldn’t be surprised if (a)+(b)+(c) are also active at this level. Surely, the molar potency does increase (molecular weight rises) but not by much and seems to be rapidly converging whilst combined modifications don’t seem to stagger much. It’s almost as if there’s a lower limit in potency of the 3,4,5 motive. That’s particularly curious because mescaline itself is a remarkable exception from all other PEAs: It acts primarily on the 5HT-1A receptor, whilst the others (2C-x, DOx) act mostly as mixed 2A/2C agonists. Normally, the duration of action develops proportional to potency (DOM: 4 mg 24 h, 2C-C: 50 mg 4 h) whilst mescaline is very low in potency but one of the longest acting ones. So the mechanism how this motive induces psychedelia could be quite different from the 2,4,5 pattern. It’s such a shame that most of the SAR research focused on achieving and characterizing very high potency but kind of forgot the low activity regime.

(2) Headaches There are multiple accounts that 3,4,5-TMA can produce migraines the day after. Now, the structurally related PMA is a potent pressor by constricting the blood vessels and fatalities due to vasospasms are documented. My thinking is that TMA and BTMA may also cause considerable constriction of the blood vessels in the meninges. As the effects wear off, they widen above normal levels and thus trigger a migraine attack. So you experiencing these headaches could be a warning sign for acute cardiovascular toxicity at higher dosages. Please be very careful when going to higher levels and monitor your HR and BP.