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Are psychedelic amphetamines toxic or anything?

An Iz

An Iz

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Sorry if this post is too dumb and newbish or if I should know to search somewhere first.

But I was wondering if you guys had any thoughts about the intersection of common psychedelic amphetamines and 'toxicity'.

I mean drugs like DO- C, M, I, and B.

I ask because I recently heard stimulants which affect serotonin can bind on the heart and hurt it somehow. Although I don't understand what I just typed I was hoping someone here might, or that they might possibly assume I did and talk some theory or memories about a paper they read? I saw a poster about using DOI to study something when I was in school, so I assume people must know some things about that class of chemicals.

Thanks.
 
Sort of. Unlike LSD or most tryptamines or two carbon phenethylamines, these drugs are well known to be 5HT2A full agonists as opposed to partial agonists. Aside from and possible relating to that, the drugs appear to be more dangerous: there are reports of deaths ascribed to DOB, DOI and DOB-Fly. They appear to be inherently more vasoconstrictive than many other psychedelics.

Many serotonin agonists bond all over the body, see: http://en.wikipedia.org/wiki/5-HT_receptor

The primary long-term receptor of concern for cardiovascular toxicity is 5HT2B agonism, but the dangerous of this usually is only apparent after prolonged chronic administration
 
nuke said:
The primary long-term receptor of concern for cardiovascular toxicity is 5HT2B agonism, but the dangerous of this usually is only apparent after prolonged chronic administration
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The 5-HT2B receptor regulates cardiac structure and functions as demonstrated by the abnormal cardiac development observed in 5-HT2B receptor null mice.[5] The 5-HT2B receptor stimulation can also lead to pathological proliferation of cardiac valves fibroblasts,[6] which with chronic overstimulation of 5-HT2B can lead to a severe valvulopathy. Moreover, 5-HT2B receptors were recently shown to be overexpressed in human failing heart and antagonists of 5-HT2B receptors were uncovered to prevent both angiotensin II or beta-adrenergic agonist-induced pathological cardiac hypertrophy in mouse.[7][8][9]
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http://en.wikipedia.org/wiki/5-HT2B_receptor
 
Thank you for the reply Nuke and Enkidu.

I see this is all right there on the wiki page for cardiac fibrosis.

If I used one of those drugs daily for around a year, and actually quit because I started to feel chest pains while under the influence, what sort of steps could I take to investigate anything that may have happened?
 
see a cardiologist and tell them that you took a full 5ht2b agonist for a year - be prepared for a scolding!

aside from potential cardiotoxicity, there is some evidence in a study by dennis mckenna that at high doses they (DOM) exert MDMA type toxicity from monoamine release (but i believe the doses used in the study are too high to be relevant for human rec. use) they probably produce some degree of oxidative stress although how severe it is compared to say d-AMPH i cannot say.
 
The DOX's with halogen or alkylthio substitution at the 4 position seem to have toxicity at higher doses (halogens it's vasoconstriction, alkylthios it's MaO inhibition) as hamhurricane stated, the toxic doses od DOM (& probably all 4-alkyl derivatives) are well outside the normal human dose range; then again even surviving a large dose of DOM is going to leave you psychologically fucked if the experiences with DOM in the 60s are anything to go be (thoses doses were 30mg+ - 9mg of dOM ripped me a new one it was so intense. It did begin the process of getting rid of my ketamine addiction though!).

As the halogens are toxic at high dose, I'd assume that the pseudohalogens at 4 position (trifluoromethyl, 2-flouroethyl etc) have equal toxicity in case you have one of the more exotic examples
 
Would the 24-36 hour duration of 5-HT2B agonism be cause for concern? Or is this something that would have to be prolonged for days/weeks/months/years?

Or the 24-36 hour duration of vasoconstriction, if it is just causing a feeling of restriction in the neck and legs/arm muscles, but no purpling/tingling?
 
What about neurotoxicity? Would the DOx cause, for example, amphetamine-like toxicity or wouldn't they, as their receptor affinities differ quite a lot from plain amph?
 
immad said:
What about neurotoxicity? Would the DOx cause, for example, amphetamine-like toxicity or wouldn't they, as their receptor affinities differ quite a lot from plain amph?
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I doubt it... There was a study a little while back saying DOI was neurotoxic but they exposed the cells to an absurd amount of it, and it was a transfected cell line anyway.

Would the 24-36 hour duration of 5-HT2B agonism be cause for concern? Or is this something that would have to be prolonged for days/weeks/months/years?

Or the 24-36 hour duration of vasoconstriction, if it is just causing a feeling of restriction in the neck and legs/arm muscles, but no purpling/tingling?
Click to expand...

I don't think so, me and a lot of people I know have done large amounts of DOx without encountering heart problems... One of my friends who used to stay up on them for 3-4 days at a time said his dad loved to do the same thing when he was a kid with DOM, and they're both still alive and healthy, but that's all anecdotal. The DOxs have many fold higher selectivity for 5HT2A/2C over 5HT2B.

Binding affinities (Ki)

DOI
5HT2A: 0.70 nM (human cloned, HL 125I-DOI)
5HT2B: 20.0 nM (human cloned, HL 3H-5HT)
5HT2C: 2.40 nM (human cloned, HL 125I-DOI)

DOB
5HT2A: 0.60 nM (human cloned, HL 125I-DOI)
5HT2B: 26.9 nM (human cloned, HL 3H-5HT)
5HT2C: 1.30 nM (human cloned, HL 125I-DOI)

DOC
5HT2A: 1.40 nM (human cloned, HL 125I-DOI)
5HT2B: 31.8 nM (human cloned, HL 3H-5HT)
5HT2C: 2.00 nM (human cloned, HL 125I-DOI)

DOM
5HT2A: 21.0 nM (human cloned, HL 3H-DOB )
5HT2B: ? nM (not assayed)
5HT2C: 41.7 nM (rat cloned, HL 125I-DOI)

Source: http://pdsp.med.unc.edu
 
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Close, it's the dissociation constant for a complex (inhibition constant). It's calculated by the displacement of a substrate from a complexed enzyme (EG labled 5HT), with the following formula if you have the IC50:
38b873f0.gif


There's more info here: http://www.curvefit.com/inhibitors.htm

And yes, smaller values indicate greater affinity for the receptor.
 
My reasoning is simply because they've caused greater fatalities per use than all the other partial agonists, and they all have full agonism in common. For instance, LSD and psilocybin and pretty much all the halogenated and alkylated 2c-? drugs and mescaline have seldom ever caused deaths, while there are several cases of deaths from the much less abused DO?s and DOB-Dragonfly.
 
So a clear correlation sans mechanism? any likely confounds in this relationship, eg adrenergic agonism or the like? Any speculations as to the mechanism?

I'm not skeptical, just curious...

ebola
 
We know para-chlorinated amphetamines do harm (mainly other than p-FA) serotonergic cells, does 2,5-dimethoxy substituation remove this neurotoxicity?
 
i was just reading a paper called "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain" which tested the monoamine releasing effects of 2C-I/E/C none of them had any effects on monoamine release EXCEPT 2C-C which was a weak Norepinephrine releaser, this makes me wonder if DOC possesses a unusual monoamine releasing effect not common among the other DOx series.


The effects of drugs on monoamine release from rat brain synaptosome
Drugs Release (EC50, M)(a)
Dopamine 5-HT Norepinephrine
2C-I n.e. n.e. n.e.
2C-E n.e. n.e. n.e.
2C-C n.e. n.e. 1.0 ± x10− 4
Click to expand...
 
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