Pharmacology - MAOI's and 2C-T-2, 2C-T-7, & 2C-T family

Discussion in 'Phenethylamines' started by B;ack_Ninja, Nov 21, 2005.

  1. B;ack_Ninja

    B;ack_Ninja Newbie

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    Mod Edit:Thread was completely off topic and went nowhere until it went off-topic again and onto the subject of MAOI's and the 2c-t family specifically, and 2 the 2c family to a lesser extent- so OP has been hijacked. ~TF~ (another thread/posts from another thread on this same tpic have also been merged in)
     
    Last edited by a moderator: Nov 2, 2010
  2. fastandbulbous

    fastandbulbous Titanium Member

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    Last edited by a moderator: Nov 2, 2010
  3. Nagognog2

    Nagognog2 Iridium Member

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    If that be the case, and 4-thio's exhibit MAOI activity, I'd advise against mixing them with an entire shopping list of molecules. Good catch, F&B.
     
  4. nanobrain

    nanobrain Platinum Member

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    thanks F&B, this puts a new spin on polycombining with irreversible MAOBIs....

    y'all reckon MAOA inhibition takes place with 4-2-fluoroethylthio as well?
     
  5. fastandbulbous

    fastandbulbous Titanium Member

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    I'd say it's pretty likely. If you consider that 4-MTA shows competetive inhibition of MAO-A as well as 2C-T-7 etc, I'd say it looks like anything with a 4-alkylthio group attached will occupy the active site of MAO-A and stop it working.


    I've got a (somewhat flakey) theory as to why this happens: Sulphur is in the same periodic group as oxygen and other than it's size does a good job of replacing oxygen in molecules (similar elect. config). The 3-methoxy-4-alkylthio bit of 2C-T-x's is similar to catecholamines that normally get chewed up by MAO; so 2C-T-x's (& aleph family) fit into the active site, but because of the fact that sulphur doesn't have two lone pairs of electrons in the way oxygen does, it doesn't bind 'correctly' and therefore doesn't get the full enzymatic degredation process.





    Might be useful to see if any other 4-alkylthios have IC50's w.r.t. MAO-A


    Oh and yes, combining them with irreversible MAO-B inhibitors like selegeline wouldn't be at all big & cleverEdited by: fastandbulbous
     
  6. nanobrain

    nanobrain Platinum Member

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    ^hmmm, i'll have to dig through my MAO papers. if this is true, there's all sorts of free radical formation and membrane damage bound to be going on.

    that said, no MAO diet was followed after getting the munchies on several ventures into the 4-2-fluoroethylthio / selegeline combo territory - blue brie and avocado sandwiches, chocolate, pizza, couple glasses of StEmillion, few beers, etc...

    which i shall not repeat inlight of newly emerging evidence ^
     
  7. snapper

    snapper Gold Member

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    Well, MAOI-A activity would explain the some of the unpredictable side effects of 2-ct-7, though I doubt it is the whole story. In spite of all the hype, even the strong MAOI inhibitors are quite forgiving given their availability and use. And just because such activity is published, does not mean it occurs in vivo to any significant extent. 2-ct-7 does not seem to potentiate tryptamines like harmine does, though it is difficult to tell in the background of 2-ct-7's effects.

    Snapper
     
  8. Nagognog2

    Nagognog2 Iridium Member

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    Do you know of any study of people given 2-CT-7, or similar, and then given an oral dose of DMT? If so - tell me where. Sounds like a nice country.
     
  9. fastandbulbous

    fastandbulbous Titanium Member

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    The relevant paper with the MAOI info is:-

    Monoamine Oxidase Inhibitory properties of some methoxylated and alkylthio amphetamine derivatives. Biochemical Pharmacology Vol. 54, pp1361-1369, 1997
     
  10. snapper

    snapper Gold Member

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    No study, but subjective accounts from Mars indicate that tryptamines pretty much have the same potency in tandem with 2-CT-7. This is on Mars, mind you. As I was led to understand, combinations included 5meoDIPT, DPT, psilocin, but none of non-oral availability..
    No very scientific at all

    Snapper
     
  11. snapper

    snapper Gold Member

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    MAOI activity of 2C-T-x series compounds

    I tried to find the reference discussing these findings, but failed. The NCBI link posted in another thread didn't work.

    However, I can say that MAOI effects have been absent in practice when combined with tryptamines of various sorts. In vitro activity does not always translate to in vivo activity, if that was the way MAOI-a activity was assessed. I think the big problem with 2-CT-x, esp. 7, is related to arrythmias and cardiac arrest. Unlike most other phens I have tried, 2-ct-7 causes lots arrythmias. One could easily see this becoming problematic at higher doses and contributing to a sudden death episode.

    On another note, AMT, and even more so 5meo-AMT are MAOIs in my previous assays with other tryptamines, though I know of no official studies which document this. If someone has a reference for this, it would also be interesting...

    SNAPPER
     
  12. nanobrain

    nanobrain Platinum Member

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    appears invitro to invivo translation does impart a loss of inhibitory activity. never noted much, unless in experiments w/selegeline and 2C combos, which you shoulod never try at home.
     
  13. snapper

    snapper Gold Member

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    Well, selegeline is a MAOI, though not as effective as betacarbolines I think. Anyone have any 'in-vivo' support for MAOIs with the thio-substituted ?

    Snapper
     
  14. gib

    gib Newbie

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    phenethylamines and MAOIs

    Several sources inform me that 2C-T-7 and 2C-T-21 are MAOIs. Sources also inform me that this is true of all the 2C-T's.

    If this is true, how much can it be generalized to all the phenethylamines (2C's)? If it can't, are there any particular 2C's that one should watch out for?

    Of those that can be classified as MAOI's, would it be recommended (imperative?) that one observe a diet similar to that which accompanies an ayahuasca trip?
     
  15. Phenoxide

    Phenoxide Super Moderator

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    Re: phenethylamines and MAOIs

    I believe the evidence that the 2C-T-x subfamily are MAO inhibitors largely comes from this excellent publication from the Nichols lab:

    Sulfur-substituted alpha-alkyl phenethylamines as selective and reversible MAO-A inhibitors: biological activities, CoMFA analysis, and active site modeling

    To summarize their findings, they tested a range of different ring substituted phenethylamines with sulfur-containing groups at the 4' (para) ring position.

    They found that 4' groups containing sulfur (as is the case for the 2C-T-x group) display pronounced MAO-A inhibition, though not MAO-B inhibition. The longer of the alkyl sidechain beyond the thiol (sulfur) residue, the greater the inhibitory effect. On that basis, one could speculate that 2C-T-7 has a stronger MAO-A inhibiting effect than 2C-T-2 for example.

    They go on to demonstrate that the thiol residue likely interacts with a cysteine sidechain in the active site of the MAO-A enzyme, effectively blocking the enzyme's ability to function. The longer alkyl chains help to orientate and hold the drug in the binding pocket, allowing for stronger inhibition. Phenethylamines with 4'-sidechains starting with an oxygen residue (e.g. alkoxy sidechains) would presumably also display this effect, though Nichols speculates that it is likely to be stronger with thiols.

    It's worth noting that these tests were done on the alpha-methylated equivalents of the 2Cs; the DOx amphetamines. It may be that the amphetamines do not behave the same as their 2C equivalents in respect to MAO inhibition. However anecdotal evidence on overdose risk seems to suggest that 2C-T-x do display significant MAO inhibition.

    So basically to get back to your original question; this property cannot be considered significant for all 2Cs. It is only known to be significant where the 4' sidechain starts with sulfur or oxygen, and becomes more powerful the longer the chain beyond this residue.

    The upshot of this is that the 2C-T-x family are the only commonly available phenethylamines with this MAOI property. It would be wise to avoid any significant MAO-A inhibiting foods in the lead-up to using these compounds. More importantly one has to be much more careful with dosing, as the safety window will be far narrower. Start very conservatively, and don't ever go for heroic doses with these guys.
     
  16. gib

    gib Newbie

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    Re: phenethylamines and MAOIs

    Thanks for that very useful information Phenoxide.

    Perhaps you can answer another question for me. If the 2C-T's are MAOI's, does this not conflict with the more general fact that phenelthylamines are inhibited by natural MAOs in the body? So the 2C-T's are inhibited by, but also inhibitors of, MAOs.