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N&PD Moderators: Skorpio | someguyontheinternet
The Big and Bangin' Pseudo-Advanced Drug Chemistry, Pharmacology and More Thread, V.2
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cannibalsnail
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On a similair note:
http://en.wikipedia.org/wiki/Dexoxadrol
http://en.wikipedia.org/wiki/Etoxadrol
Potential new, non aryl-cyclohexamine dissociatives. However some worrying reports are on the page: "In the brain, etoxadrol slows down the synthesis of serotonin to 50-60% of control rates and speeds up the rate of dopamine synthesis by up to 200% of the normal rate 4–6 hours after intravenous administration". I'm unclear on what in the structure causes this but at a guess the Dioxy ring ring looks suspect: The MD ring in MDMA inhibits Tryptophan Hydroxylase and the Dopamine synthesis would be caused by a blockade of Autoreceptors on the surface membrane of Dopamine neurones.
Alternatively:
http://en.wikipedia.org/wiki/Dextrallorphan
http://en.wikipedia.org/wiki/Dextrorphan
Analogues of these could hold potential. However I think the sheer number of possible ring substitutions would make it a fumble in the dark to find anything with real activity. Maybe Acetoxy-DXO?
http://en.wikipedia.org/wiki/Dexoxadrol
http://en.wikipedia.org/wiki/Etoxadrol
Potential new, non aryl-cyclohexamine dissociatives. However some worrying reports are on the page: "In the brain, etoxadrol slows down the synthesis of serotonin to 50-60% of control rates and speeds up the rate of dopamine synthesis by up to 200% of the normal rate 4–6 hours after intravenous administration". I'm unclear on what in the structure causes this but at a guess the Dioxy ring ring looks suspect: The MD ring in MDMA inhibits Tryptophan Hydroxylase and the Dopamine synthesis would be caused by a blockade of Autoreceptors on the surface membrane of Dopamine neurones.
Alternatively:
http://en.wikipedia.org/wiki/Dextrallorphan
http://en.wikipedia.org/wiki/Dextrorphan
Analogues of these could hold potential. However I think the sheer number of possible ring substitutions would make it a fumble in the dark to find anything with real activity. Maybe Acetoxy-DXO?
JackiesBabyy
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How, in detail, does serotonin release cause empathy?
From what I can find apparently 5-HT1a being activated releases oxytocin which causes empathogenic effects. But is there more to it than that? I think you need dopamine release along with 5-HT release to cause empathy, but then why doesn't a dopamine releaser + a 5-HT1a agonist drug cause empathy? Or a dopamine releaser + an SSRI? (I know SRAs aren't SSRIs but they seemingly have the both end result, more serotonin available to bind to the receptors.)
Semi-related question, are there any selective SRAs out there? If so, what are the effects? I did read something interesting about cocaine still being reinforcing in lab mice with no dopamine transporters (cocaine is an serotonin-NE-dopamine reuptake inhibitor, and those rats still found it reinforcing with no dopamine transporter to inhibit, but this doesn't quite answer my question as it's a reuptake inhibitor and not a releasing agent).
From what I can find apparently 5-HT1a being activated releases oxytocin which causes empathogenic effects. But is there more to it than that? I think you need dopamine release along with 5-HT release to cause empathy, but then why doesn't a dopamine releaser + a 5-HT1a agonist drug cause empathy? Or a dopamine releaser + an SSRI? (I know SRAs aren't SSRIs but they seemingly have the both end result, more serotonin available to bind to the receptors.)
Semi-related question, are there any selective SRAs out there? If so, what are the effects? I did read something interesting about cocaine still being reinforcing in lab mice with no dopamine transporters (cocaine is an serotonin-NE-dopamine reuptake inhibitor, and those rats still found it reinforcing with no dopamine transporter to inhibit, but this doesn't quite answer my question as it's a reuptake inhibitor and not a releasing agent).
sekio
Bluelight Crew
MDAI is considered to be a "selective serotonin releasing agent".
I think the effects you are referring to come from the broad downstream activation of serotonin receptors.
There is no one receptor that produces "empathy" in the brain, however. As you probably realize, selective 5-HT1a agonists aren't considered to be abusable or euphoric per se.
That's some pretty interesting thinking. I don't think chemistry works that way, or Cialis (which has methylenedioxy ring on it) would be just as damaging.
It's not the structural motifs in the chemical that decide its activity; its how those motifs interact with the drug's targets that matter. The MD ring on MDMA just makes the molecule look "enough" like serotonin that it binds 10x better than "normal" amphetamine. If you put it anywhere else it doesn't work half as well.
Etoxadrol has been high on my list of "promising dissociatives". It's potent (a "recreational" dose would be likely 0.25-0.5 mg/kg), relatively long-lasting, (probably) orally bioavailiable, and most importantly it's self administered in monkeys. Not to mention its a nice painkiller etc, and any drug that has trials stopped due to hallucinations and nightmares is obviously pretty effective as a psychotropic. (Dex and etoxadrol were developed as intravenous anesthetics.)
I think the effects you are referring to come from the broad downstream activation of serotonin receptors.
There is no one receptor that produces "empathy" in the brain, however. As you probably realize, selective 5-HT1a agonists aren't considered to be abusable or euphoric per se.
That's some pretty interesting thinking. I don't think chemistry works that way, or Cialis (which has methylenedioxy ring on it) would be just as damaging.
It's not the structural motifs in the chemical that decide its activity; its how those motifs interact with the drug's targets that matter. The MD ring on MDMA just makes the molecule look "enough" like serotonin that it binds 10x better than "normal" amphetamine. If you put it anywhere else it doesn't work half as well.
Etoxadrol has been high on my list of "promising dissociatives". It's potent (a "recreational" dose would be likely 0.25-0.5 mg/kg), relatively long-lasting, (probably) orally bioavailiable, and most importantly it's self administered in monkeys. Not to mention its a nice painkiller etc, and any drug that has trials stopped due to hallucinations and nightmares is obviously pretty effective as a psychotropic. (Dex and etoxadrol were developed as intravenous anesthetics.)
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pharmakos
Bluelighter
Haha, I think that you can talk about Tocris and Sigma, the cat might be out of the bag thereOf course, I might be wrong, I don't mod this forum, but I imagine it's OK.
you'd have to be pretty rich and desperate to order your drugs from Sigma. the markups are ridiculous there.
please edit if this price discussion isn't allowed, but.... a single dose of MDA from Sigma-Aldrich would cost about $1000. for a single dose. lolol.
You're not allowed to source or even discuss vendors on this site
You should delete the first part of your post.
Welcome to Bluelight
![:\](https://bluelight.org/xf/BL_Images/Orig_Emoji/wrygrin.gif "wry grin :\")
I thought that rule only applied to RC vendors, not the major players on the field who only deliver to legit companies after going through your life history.
Epsilon Alpha
Bluelighter
Yep, these guys are ok to post!
Now where did I put my $500 kilo of NaCl from Sigma...
naughtynicknails
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amanitadine
Bluelighter
Continuing off topic, sigma, and later sigma Aldrich, as well as dudes like Acros, fisher, etc, used to be so much more accessible. Never an issue opening accounts in the early and mid 90's. Always a good source (back then) for tryptamines, ketamine, and VERY occasionally phenethylamines, including some very rare psi 2-C's, which WERE outrageously priced. But yeah, reagents, glass, you name it, were easy as cake up until the late 90's. Oh my how things have changed.. .
There has been considerable interest in etoxadrol amongst a few for a spell. I have yet to hear of any bonafide rogue trials. . . .
There has been considerable interest in etoxadrol amongst a few for a spell. I have yet to hear of any bonafide rogue trials. . . .
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doppelgänger1
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Is 4-fa metabolized in the same way and ratios as plain amphetamine, just without 4'-hydroxylation, which according to wikipedia is minor anyway?
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Let's say someone got ahold of about a gram of racemic 1,2-diphenyl-1-dimethylaminoethane hydrochloride (of confirmed identity, no vendors of questionable morals involved). If I understand correctly from the sparse information I've seen, the dextro-isomer counteracts the opioid affinity of the levo-isomer (lefetamine) somewhat. The compound is supposed to be a stimulant and act at least partly as an NMDA antagonist (from which I suppose dissociative action?)
I'm a good chemist but not that well versed in pharmacology. What would be a reasonable dosage level to try this compound, and I find it hard to picture the kind of effect it would give?
Also, racemic 1,2-diphenyl-1-piperidinoethane can be obtained, but is there any information towards the active dosage, duration and what to expect of activity in humans? I'm afraid the only experience with a dissociative I've had was a single 600mg dose of DXM, which was a bit too potent and long-lasting to my taste?
I'm a good chemist but not that well versed in pharmacology. What would be a reasonable dosage level to try this compound, and I find it hard to picture the kind of effect it would give?
Also, racemic 1,2-diphenyl-1-piperidinoethane can be obtained, but is there any information towards the active dosage, duration and what to expect of activity in humans? I'm afraid the only experience with a dissociative I've had was a single 600mg dose of DXM, which was a bit too potent and long-lasting to my taste?
sekio
Bluelight Crew
Judging from the structure and related compounds (lefetamine), I suggest titrating up to 10-30mg slowly?
cannibalsnail
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Standard safe procedure is:
~1mg on skin surface - wait 24 hours
~0.1mg orally - wait 24 hours
~0.1mg sublingualed - wait 24 hours
~0.5mg orally - wait 24 hours
~1mg orally - wait 24 hours
Then progress in 1mg increments orally or nasally every few hours until activity is reached.
~1mg on skin surface - wait 24 hours
~0.1mg orally - wait 24 hours
~0.1mg sublingualed - wait 24 hours
~0.5mg orally - wait 24 hours
~1mg orally - wait 24 hours
Then progress in 1mg increments orally or nasally every few hours until activity is reached.
Lisdexamphetamine (Vyvanse) Metabolite Hydroxyamphetamine and Lower Dopamine Levels
Not a Pharm major by any means, but pharmaceuticals is something that interests me greatly, I am currently an 11th grader, but plan to go onto pharmacy school. I do know quite a bit though. Anyways that's all the background info that's really necessary.
I read long ago about the metabolism of lisdexamphetamine (I take 60 mgs). It gets metabolized into D-Amphetamine in the body, and then roughly 95% of the D-Amphetamine is metabolized into phenylacetone, then to benzoic acid, and then finally hippuric acid. The other 5% gets converted into p-Hydroxyamphetamine,while although a minor metabolite, may have significant physiological effects as it is an analogue of norepinephrine.
"Although p-hydroxyamphetamine is a minor metabolite (~5% of the dose), it may have significant physiological effects as a norepinephrine analogue"
From: http://en.wikipedia.org/wiki/Dextroamphetamine
Coming across this next bit of inforation made me start to do some digging.
Hydroxyamphetamine is known to bind to the TAAR-1 receptors in humans, and as I read here : "Activation of rat TAAR1 expressed in HEK293 cells assessed as accumulation of [3H]cAMP after 1 hr by competitive binding assay "
source: http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=635290#aDescription
Does this have the same effect in humans with increased cAMP levels? I was wondering if this could be the cause of what i will later discuss.
I have read that increased cyclic adenosine monophosphate reduce your dopamine levels. "Another side-effect of high cAMP levels, is decreased dopamine activity and increased prolactin levels. "
source: http://voices.yahoo.com/negative-effects-high-cyclic-amp-levels-11299662.html
Although this is not the most scholarly of sources, I do believe that they wouldn't misrepresent conclusions of tests/experiments.
My step-brother is prescribed Vyvanse and Paroxetine, and I found out he was put on Paroxetine (SSRI) after being put onto Vyvanse. Paroxetine inhibits cytochrome P450 2D6 (CYP2D6), which does not allow any of the D-amphetamine to be metabolized into Hydroxyamphetamine. Could the Hydroxyamphetamine have caused (through increased cAMP levels) lower dopamine levels while there was still a buildup of cAMP before the effects of the Hydroxyamphetamine go away, and thus contributed to some depression-like symptoms? I do know that CNS stimulants/amphetamines usually cause higher dopamine levels (which are generally naturally lower in people with ADHD), but is the deficit caused by the hydroxyamphetamine enough to offset the gain in dopamine caused by Dextroamphetamine. Could this be a reason why he developed minor depression like symptoms or his already current symptoms (I don't know which was the case) worsened or did not improve after starting vyvanse? Or could this have been perscribed in response to anxiety onset by the Hydroxyamphetamine? Could Paroxetine then be considered as a booster such as Intuniv (guanfacine) to increase the duration of the drug and lower anxiety/other adverse affects? Any input would be greatly appreciated as I am very curious!
Not a Pharm major by any means, but pharmaceuticals is something that interests me greatly, I am currently an 11th grader, but plan to go onto pharmacy school. I do know quite a bit though. Anyways that's all the background info that's really necessary.
I read long ago about the metabolism of lisdexamphetamine (I take 60 mgs). It gets metabolized into D-Amphetamine in the body, and then roughly 95% of the D-Amphetamine is metabolized into phenylacetone, then to benzoic acid, and then finally hippuric acid. The other 5% gets converted into p-Hydroxyamphetamine,while although a minor metabolite, may have significant physiological effects as it is an analogue of norepinephrine.
"Although p-hydroxyamphetamine is a minor metabolite (~5% of the dose), it may have significant physiological effects as a norepinephrine analogue"
From: http://en.wikipedia.org/wiki/Dextroamphetamine
Coming across this next bit of inforation made me start to do some digging.
Hydroxyamphetamine is known to bind to the TAAR-1 receptors in humans, and as I read here : "Activation of rat TAAR1 expressed in HEK293 cells assessed as accumulation of [3H]cAMP after 1 hr by competitive binding assay "
source: http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=635290#aDescription
Does this have the same effect in humans with increased cAMP levels? I was wondering if this could be the cause of what i will later discuss.
I have read that increased cyclic adenosine monophosphate reduce your dopamine levels. "Another side-effect of high cAMP levels, is decreased dopamine activity and increased prolactin levels. "
source: http://voices.yahoo.com/negative-effects-high-cyclic-amp-levels-11299662.html
Although this is not the most scholarly of sources, I do believe that they wouldn't misrepresent conclusions of tests/experiments.
My step-brother is prescribed Vyvanse and Paroxetine, and I found out he was put on Paroxetine (SSRI) after being put onto Vyvanse. Paroxetine inhibits cytochrome P450 2D6 (CYP2D6), which does not allow any of the D-amphetamine to be metabolized into Hydroxyamphetamine. Could the Hydroxyamphetamine have caused (through increased cAMP levels) lower dopamine levels while there was still a buildup of cAMP before the effects of the Hydroxyamphetamine go away, and thus contributed to some depression-like symptoms? I do know that CNS stimulants/amphetamines usually cause higher dopamine levels (which are generally naturally lower in people with ADHD), but is the deficit caused by the hydroxyamphetamine enough to offset the gain in dopamine caused by Dextroamphetamine. Could this be a reason why he developed minor depression like symptoms or his already current symptoms (I don't know which was the case) worsened or did not improve after starting vyvanse? Or could this have been perscribed in response to anxiety onset by the Hydroxyamphetamine? Could Paroxetine then be considered as a booster such as Intuniv (guanfacine) to increase the duration of the drug and lower anxiety/other adverse affects? Any input would be greatly appreciated as I am very curious!
sekio
Bluelight Crew
Hydroxyamphetamine does not cause "lower dopamine levels", you are reading much too far into this...
the effects of elevated cAMP are too broad... its one of the well studie intracellular messengers. i think only *chronically high* levels of camp cause dopamine downregulation. (not acute stimulant effects)
and you forget that amphetamine itself is a ligand for the TAAR.... really amphetamine has the same effects as hydroxy-amphetamine, it is just more polar and lacks the same degree of central effects as it cannot cross the blood brain barrier so effectively.
the effects of elevated cAMP are too broad... its one of the well studie intracellular messengers. i think only *chronically high* levels of camp cause dopamine downregulation. (not acute stimulant effects)
and you forget that amphetamine itself is a ligand for the TAAR.... really amphetamine has the same effects as hydroxy-amphetamine, it is just more polar and lacks the same degree of central effects as it cannot cross the blood brain barrier so effectively.
I figured as much, for a medicine that inefficient, wouldn't do much good. But sill on this topic, would this cause the vyvanse to last slightly longer, due to it having to all be metabolized one way, where the rate of metabolization would be slightly lower. Also do you anything about the facilitation of L-Lysine removal, by reflux in a very basic solution? Then one could neutralize the solution (say NaOH and HCl) and end up with salt, d-amp, and L-Lysine. Then one could boil off the water, then put
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I figured as much, for a medicine that inefficient, wouldn't do much good. But sill on this topic, would this cause the vyvanse to last slightly longer, due to it having to all be metabolized one way, where the rate of metabolization would be slightly lower?
Also do you know anything about the facilitation of L-Lysine removal, by reflux in a very basic solution? I vaguely remember hearing something about it. Just thinking here, but if it's possible, then one could neutralize the solution (say NaOH and HCl) and end up with salt, d-amp, and L-Lysine. Then one could evaporate/ boil off the water, then put the dry contents in acetone and remove insolubles and repeat process. This would leave you with pure L-Lysine and Dextroamphetamine? Just curious for educational purposes, I've seen a lot of people discussing trypsin as a method. For one that could obtain such chemicals this would be a simple alternative.
I figured as much, for a medicine that inefficient, wouldn't do much good. But sill on this topic, would this cause the vyvanse to last slightly longer, due to it having to all be metabolized one way, where the rate of metabolization would be slightly lower?
Also do you know anything about the facilitation of L-Lysine removal, by reflux in a very basic solution? I vaguely remember hearing something about it. Just thinking here, but if it's possible, then one could neutralize the solution (say NaOH and HCl) and end up with salt, d-amp, and L-Lysine. Then one could evaporate/ boil off the water, then put the dry contents in acetone and remove insolubles and repeat process. This would leave you with pure L-Lysine and Dextroamphetamine? Just curious for educational purposes, I've seen a lot of people discussing trypsin as a method. For one that could obtain such chemicals this would be a simple alternative.
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