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I Like to Draw Pictures of Random Molecules

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GyUj7.png

This chappy? Don't know much about pharmacology but that seems way polar and bulky, ebola? or someone, are we even talking about stimulant SAR here? I feel like I'm very negative in this thread, I'm sorry, it's probably the manifestation of insecurity. Live the dream, be the change, have a Chinese national synthesise it. By the way, Dresden, I've said it before, you may just be on a phone or tablet or something, but ISIS/Symyx/Accelerys (I think it's all basically the same program, I'm unsure, it's not important) is free and serviceable, not quite as good as Chemdraw, but free and perfectly good with a little practice, you can get it here, it can draw anything you'd want, generate structures from text/SMILES and vice versa, worthwhile.
 
That ester will readily hydrolyse and leave you with something that will be very rapidly excreted. Additionally, it is unlikely to be active with such a polar substituent preventing BBB permeation.
 
I got the aryl carbomethoxy idea from a new phenylethylamine nootropic which has a thread around here somewhere and also shares the Ar-3-CO2CH3. I don't recall its name though, sorry.

Think of 3-CO2CH3 methcathinone as a more electronegative 3-MMC. And then, of course, there is the possibility of the 4-CO2CH3 isomer.

If methylphenidate is any guide, the CO2CH3 moiety should last at least 2 to 4 hours.
 
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Cathinones seem to display much less neurotoxicity. Presumably this is metabolite mediated as the B-ketone provides a "weak-point" which is easily metabolised to allow excretion and therefore this limits the potential to form dangerous metabolites through other routes cf. methylone, mephedrone
 
Methcathinone and methylone were threefold less potent than MA or MDMA at inhibiting [3H]5-HT uptake into human platelets, with IC50's of 31.4 ± 7.3 uM and 5.8 ± 0.7 uM, respectively. In C6 glial cells stably expressing the rat dopamine transporter, methcathinone and methylone were similar in potency to MA and MDMA, with IC50's for [3H]DA uptake of 0.36 ± 0.06 uM and 0.82 ± 0.17 uM, respectively. Methcathinone and methylone were also similar in potency to MA and MDMA in C6 cells expressing the human norepinephrine transporter, with IC50's for [3H]NE accumulation of 0.51 ± 0.10 uM and 1.2 ± 0.1 uM, respectively. The benzylic ketone moiety of methcathinone and methylone had a large (tenfold) negative impact on the abilities of these drugs to inhibit the vesicular monoamine transporter (VMAT2) compared to MA and MDMA.

So, we see that the simple addition of a beta-ketone moiety to a PEA which normally had affinity for the VMAT2 drops the new compound's ability to interact with that receptor by 1000%!

For those unaware of the rather large implications of this:
VMAT2 is essential in the presynaptic neuron's ability to facilitate the release of neurotransmitters into the synaptic cleft.
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Therefore it seems these compounds, methcathinone and methylone [being literally 10x less efficient at interfacing with this receptor when compared to their monoamine releasing homologues methamphetamine and MDMA] are primarily re-uptake inhibitors, as they cannot bind to the VMAT2 with sufficient force as to facilitate release. Furthermore, these findings can almost certainly be applied to all the beta-keto compounds.

Got a knowledge bomb or two up my sleeve. Since we can assume brephedrone doesn't activate VMAT2, and therefore is a simple reuptake inhibitor, our conclusion regarding it's toxicity becomes increasingly clear. Drugs which only reuptake monoamines are generally much more benign as far as neurotoxicity. Even during simultaneous and strong serotonin release via MDAI, co-administration of a simple DARI resulted in *no* neurotoxicity. And THAT's straight from Nichols.
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From here. I don't know much credence to give it, but it was brought up in a discussion of brephedrone. It's essentially a bit beyond me, take it with a megadalton of halite.
 
I know I sound annoying, but that al-lsz thing I posted a few pages back and the mapdbs are definitely something I'd like to see sold. If only I were rich and could just pay for having all sorts of weird chemicals I wanted ....
 
Therefore it seems these compounds, methcathinone and methylone [being literally 10x less efficient at interfacing with this receptor when compared to their monoamine releasing homologues methamphetamine and MDMA] are primarily re-uptake inhibitors, as they cannot bind to the VMAT2 with sufficient force as to facilitate release. Furthermore, these findings can almost certainly be applied to all the beta-keto compounds.
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mmm...I don't see how a compound that effects transporter reversal with high efficacy could function primarily as a reuptake inhibitor though. It might be less effective in maintaining tonic synaptic monoamine concentration increase in comparison to compounds that have significant affinity for VMAT2, but it's still different from mere reuptake inhibition. Furthermore, controlling for general potency, another study found mephedrone to be highly effective at increasing synaptic monoamines, rivaling MDMA and amphetamine. Methcathinone has also been observed to cause neurotoxicity qualitatively similar to methamphetamine though with reduced magnitude.

Since we can assume brephedrone doesn't activate VMAT2, and therefore is a simple reuptake inhibitor, our conclusion regarding it's toxicity becomes increasingly clear.
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No, it doesn't. The specific mechanisms underlying the toxicity of PCA are unknown, beyond the fact that binding at SERT is necessary for such neurotoxic effects. They seem somewhat distinct from those of other entactogens, as PCA exerts greater toxicity than MDMA at similar levels of serotonergic efflux.

ebola
 
Yeah, like I say, I'm not in any way able to critically evaluate those claims. They are not mine and I do not hold or advocate them. I was just reminded of this.
Methcathinone has also been observed to cause neurotoxicity qualitatively similar to methamphetamine though with reduced magnitude.
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Is this in clinical trials with pure compounds, or in street users? Only 'cos it seems like KMnO4 toxicity would be common in mcat users.
 
lulz

So I've hit a weird stride of finding novel RCs for sale. Earlier, 5-bromo-DMT and 5-isopropyl-DMT, pretty odd. Then, I said in EADD that no, I hadn't heard rumours of another lysergamide RC, and moments later, happened across a vendor offering "Lysergic acid 2-butylamide":
AUdzn.png

(My skeletal formulas, apologise if I've made a mistake, I'm so tired I just spent longer than I should scanning the list of forums, bemusedly unable to find Advanced Drug Discussion). It seems that AL-LAD and LSZ are definitely being sold, isobutylysergamide (I've just made that name up) is allegedly available, and the higher homologues of LSD seem to be natural candidates. LiHKAL, anyone?
 
Ok guys, here's one for you. I was thinking the other day about how much I really enjoy a mix of 2C-T-2 and 2C-T-7, and how that together they are more than the sum of their parts. I find the blend to be very entactogenic, and EXTREMELY visual. The compounds also potentiate each other, so that a dose of about 10mg of each is a very powerful and ecstatic experience, with a profoundly spiritual component being a semi-regular occurrence at this dose.

Since this combination is so enjoyable to me, I got to thinking, why not design a compound that could bring the experience of both? The most obvious way to do this, in my mind anyway, was an ester. However, there are no free hydroxyl groups in either compound. This brought me to the HOT series. I have as yet very limited experience with these compounds, but from my limited trials of each, I find them to be very comparable to their N-deshydroxy counterparts. So, without further ado, a compound that should break down to form HOT-2 and HOT-7 in vivo:

HOT-2-SO4-HOT-7diester.png


And here is a similar one for HOT-4 and HOT-7 that I did just for the hell of it as well:

HOT-4-SO4-HOT7diester.png


Thoughts, anyone?
 
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DUH!! Hahaha, I posted the wrong file! This was just another one I was messing with for fun. I'm going to update that to the right one right now.

EDIT: Ok, there we go! Thanks for pointing that out babylonboy!
 
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Wouldn't that be potentially dangerous given the difference in dosage the two have and that 2C-T-7 is likely an MAOI?

I personally am so sensitive to 2C-T-7 that 15mg had me drifting in and out of consciousness while I have taken 38mg of 2C-T-2 and still kept my wits about me.

Cool idea though.
 
I have taken them together quite a few times and I've been fine. Like I said in the post though, I've never exceeded 10mg of each as a dose. There is definitely potentiation going on there, but the effects are much more magical and mystical than they are apart. I have yet to try mixing HOT-2 and HOT-7, but I imagine it will work in a similar way, given the fact that, in myself at least, the HOT-X series seems very similar to their 2C-T-X counterparts. There's also the fact that this would be a totally dissimilar compound from a legal perspective...
 
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