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The Large and Nifty Not-quite-advanced Drug Chemistry, Pharmacology and More Thread

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I assume you are interested in attenuating potentially severe a1-mediated peripheral vasoconstriction and resulting tissue death caused by substituted cathinones and the like. If that's not the case, then my apologies. Anyway, I suppose any a1 blocker will due, say prazosin- I'm not sure about BBB issues but if you are on a stimulant, a little central a1 blockade shouldn't be a big deal.

HOWEVER, I remember reading that using a1 blockers for this purpose is a bad idea because of the risk of tachycardia.
 
acetylcholine said:
I assume you are interested in attenuating potentially severe a1-mediated peripheral vasoconstriction and resulting tissue death caused by substituted cathinones and the like. If that's not the case, then my apologies. Anyway, I suppose any a1 blocker will due, say prazosin- I'm not sure about BBB issues but if you are on a stimulant, a little central a1 blockade shouldn't be a big deal.

HOWEVER, I remember reading that using a1 blockers for this purpose is a bad idea because of the risk of tachycardia.
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Thanks for the response. Actually I was asking in order to discover how to block cocaine/amphetamine-induced anxiety/agitation. Beta blockers don't work, and I doubt Benzos would be a good choice. I'm currently trying to see if a calcium channel blocker can help with Cannabis-induced anxiety and panic attacks, and I've read they can help the same problem encountered with stimulants. There has to be a direct mechanism that causes these issues with stimulants that can be taken care of without affecting the high/euphoria or causing further problems. Tachycardia could be an issue with prazosin.
 
Interesting stuff Amu. Have you seen papers suggesting this and can you link?

Are the Ca channel agents you are considering anticonvulsants like, say, gabapentin?
 
just based on the way that pregabalin felt in me, i'd say that it very likely would block amphetamine anxiety/jitters.
 
acetylcholine said:
Interesting stuff Amu. Have you seen papers suggesting this and can you link?

Are the Ca channel agents you are considering anticonvulsants like, say, gabapentin?
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http://www.ncbi.nlm.nih.gov/pubmed/18195452
http://www.ncbi.nlm.nih.gov/pubmed/11165225
http://www.ncbi.nlm.nih.gov/pubmed/9299207

http://www.ncbi.nlm.nih.gov/pubmed/2076753

Calcium channel blockers such as Verapamil can block amphetamine induced-anxiety/psychosis/aggression without affecting the primary dopamine release.

Interesting you mention Gabapentin, I haven't read any studies directly on the effects of it on amphetamine's effects, but I'm sure it would have certain positive effects.
 
Amu said:
http://www.ncbi.nlm.nih.gov/pubmed/18195452
http://www.ncbi.nlm.nih.gov/pubmed/11165225
http://www.ncbi.nlm.nih.gov/pubmed/9299207

http://www.ncbi.nlm.nih.gov/pubmed/2076753

Calcium channel blockers such as Verapamil can block amphetamine induced-anxiety/psychosis/aggression without affecting the primary dopamine release.

Interesting you mention Gabapentin, I haven't read any studies directly on the effects of it on amphetamine's effects, but I'm sure it would have certain positive effects.
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Thanks for the links!
 
what about this molecule? you could think of it as alpha-desmethyl-6-APB (edit/correction: it'd be 6-APDB the way i have it drawn, and it's not just alpha-desmethyl but also has an added oxygen at the 2-position...), but i like to think of it as 2C-E with the 4-ethyl bonded to the 5-oxygen. should there be a double bond there instead of a single? IDK i haven't even taken an O-Chem course.

anyway, what do you guys think of molecules like this in general? the sort of half-way point between the 2C family and the MDA family... could the 2-position oxygen make it so that there is empathogen activity even without the alpha-methyl? perhaps it's active as a psychedlic similar to 2C-E, 2C-D, MDA, or MMDA-2?

ivicqs.jpg


just to reiterate, in case there's any vendors out there looking at this -- i am a dumb ass when it comes to O-Chem, and this stuff very well could be a neurotoxin for all i know.

edit -- surely someone has to have dreamed up or even created this stuff somewhere at some point in time! am i correct in naming it 5-Methoxy-6-(2-Aminoethyl)-2,3-dihydrobenzofuran? i think 5-Methoxy-6-(2-Aminoethyl)benzofuran is the name of what i MEANT to draw.
 
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^ both drawings are the same molecule (I assume you are aware of that)

for hallucinogenic activity the SAR that deals with these molecules is that determined by nichols et al with the dragonflies and hemidragonflies, however the 2,4,5 hemifly excuse the numbering with the dihydrofuran ring at the 4,5 positions is not a very active 5ht2a agonist. the simple rule of thumb is you can only bend back the methoxy into a dihydrofuran into positions that do not involve the 4 position, it isn't quite as simple as that but that is the essence. it has to do with what direction the oxygen lone pairs point. if the furan is replaced with a methylenedioxy ring then there is some activity, but then perhaps the molecule is more like a 3,4,5 phenthylamine in the way it binds and they usually have slightly different binding to 2,4,5 phenthylamines at 5ht2a.

as to empathogenic activity who knows? instinct says it will be thoroughly inactive it is probably a good enzyme substrate and so gets chewed, the related methylenedioxy compound has not been properly tasted to my knowledge, shulgin briefly discusses it in pihkal.

from pihkal #133 MMDA-2
The phenethylamine analog of MMDA-2 has been prepared by the condensation of the above benzaldehyde with nitromethane (in acetic acid with ammonium acetate catalyst, giving an equal weight of the nitrostyrene as deep orange crystals with a mp of 166-167 °C from ethyl acetate) followed by lithium aluminum hydride reduction (in ether). The product, 2-methoxy-4,5-methylenedioxyphenethylamine hydrochloride (2C-2) melted at 218-219 °C. There were no effects observed at up to 2.6 milligrams, but no higher trials were made.
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I wouldn't go near this or the methylenedioxy compound because of its similarity to the neurotoxin 6-OH dopamine, which is a bit too likely to be a metabolite (by O demethylation and ring opening) , which is then followed by oxidation to some pretty nasty quinones.
 
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How come TMPEA (2,4,5-trimethoxyphenethylamine) isn't active? TMA-2 is more potent than TMA, 2C-T is active, the 2,4,5 pattern is a winner in general, I assumed that this one would be a gem but Shulgin says no activity at 300 mg. Any idea why?
 
vecktor said:
^ both drawings are the same molecule (I assume you are aware of that)

for hallucinogenic activity the SAR that deals with these molecules is that determined by nichols et al with the dragonflies and hemidragonflies, however the 2,4,5 hemifly excuse the numbering with the dihydrofuran ring at the 4,5 positions is not a very active 5ht2a agonist. the simple rule of thumb is you can only bend back the methoxy into a dihydrofuran into positions that do not involve the 4 position, it isn't quite as simple as that but that is the essence. it has to do with what direction the oxygen lone pairs point. if the furan is replaced with a methylenedioxy ring then there is some activity, but then perhaps the molecule is more like a 3,4,5 phenthylamine in the way it binds and they usually have slightly different binding to 2,4,5 phenthylamines at 5ht2a.

as to empathogenic activity who knows? instinct says it will be thoroughly inactive it is probably a good enzyme substrate and so gets chewed, the related methylenedioxy compound has not been properly tasted to my knowledge, shulgin briefly discusses it in pihkal.

from pihkal #133 MMDA-2


I wouldn't go near this or the methylenedioxy compound because of its similarity to the neurotoxin 6-OH dopamine, which is a bit too likely to be a metabolite (by O demethylation and ring opening) , which is then followed by oxidation to some pretty nasty quinones.
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thanks for the response, you've given me a lot to think about and research.

p.s. i was aware that the two drawings were of the same molecule. i just figured seeing both perspectives would help creative thinking.
 
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i hear 2methylmdma is one of the more potent and active analogs, this true? shulgin hints at it, and no one on the net seems to want to bring it up...
 
randomly thought this one up while the site was down... i can't find anything about it anywhere, but i figure Nichols must have at least thought of it...

2,5-dimethoxy-4-hexafluoroisopropylphenethylamine, 2C-HFIP

so american of me (2C-TFM is awesome with 3 fluoros out there, lets get twice as many on that 4-position! XD), but still, it made me drool a little bit when i thought it up lol ;)

any thoughts on this stuff, or on why nichols hasn't made it yet? i've also got a feeling that there's a pretty obvious answer to that question =p

oh, and i don't feel too bad about posting this chemical wankery, because i'm pretty sure that the chemistry involved in making this stuff would be prohibitively expensive enough that this will not reach the "research chemical" masses...
 
You can get 7 fluorines on an isopropyl group =D Though I'd probably rather the n-heptafluoropropyl version.

vecktor said:
I wouldn't go near this or the methylenedioxy compound because of its similarity to the neurotoxin 6-OH dopamine, which is a bit too likely to be a metabolite (by O demethylation and ring opening) , which is then followed by oxidation to some pretty nasty quinones.
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That's a good point, and I guess 6-OH-alpha-Me-dopamine is just as neurotoxic? Do you think this is a bigger issue with MMDA-2 than TMA-2, ie. is demethylenation (think it's a word!) faster than demethylation? Not that it really matters, MMDA-2's not very nice anyway; 'some not-too-pleasant jangly effects,' as the first entries in pihkal says!
 
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SSRIs work by inhibiting the reuptake mechanism of a neuron, and that results in greater serotonin activity in the serotoninergic receptors.

A serotine antagonist does pretty much the opposite, it blocks serotonin activity in the receptors.

So, since SSRIs are supposed to be antidepressants, serotonin antagonists can cause depression ? I am asking cuz most/all 2nd generation antipsychotics are serotonin antagonists, amongst others.
 
Hi.

What about N,N-dimethylphenylethylamine?
29zuh3b.jpg


Chemistry? Toxicity?
Has anyone ever tried it?

And derivatives, like N,N-dimethyl-alfa-methylphenylethylamine?

I was thinking about AMT, the "tryptamine version" of amphetamine, and wondered, why not a "phenylethylamine version" of DMT?
 
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So, since SSRIs are supposed to be antidepressants, serotonin antagonists can cause depression ?
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Apparently not. It seems that SSRIs work (insofar as they do--they are only marginally effective) via some sort of downstream effect, not generalized increase in serotonergic signalling.

ebola
 
ebola? said:
Apparently not. It seems that SSRIs work (insofar as they do--they are only marginally effective) via some sort of downstream effect, not generalized increase in serotonergic signalling.

ebola
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Ok the bold part partly answers my question.
However I read in wiki that SSREs (reuptake Enhancers) work as much as the SSRIs (reuptake inhibitors). How is that possible?

And what exactly is the downstream effect ? That would help.
 
Atypical antipsychotics usually antagonize serotonin 2A and 2C receptors, which increases signalling to all other serotonin receptors, theoretically having an antidepressant (because of increased activating of s1A receptor/anti-anxiety(2A antagonism)/antipsychotic (2C antagonism) effect.
 
Wizzle said:
Atypical antipsychotics usually antagonize serotonin 2A and 2C receptors, which increases signalling to all other serotonin receptors, theoretically having an antidepressant (because of increased activating of s1A receptor/anti-anxiety(2A antagonism)/antipsychotic (2C antagonism) effect.
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Thnx for the reply. However why antagonizing 2A and 2C results in increased activity to other serotonin receptors? It might seem kind of obvious but I would like to see it explained more analytically. Serotonin neurotransmitters can't use 2A and 2C so they use the remaining receptors? The exact same serotonin neurotransmitter can bind to any serotonin receptor?
 
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