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

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LSD changed colour in the bottle

I was given a small bottle of LSD by a VERY reliable source who said it was colourless initially (as it should be), but after ~4 months in storage (in a drawer in the dark.. 20-25 degrees Celsius approximately it has changed to a dark brown sort of colour. The bottle is made of plastic and sealed well with a plastic lid. There's about 5-6 drops in the bottle, not sure if the quantity is at all relevant. My source has taken it and has confirmed that it is LSD - they have a fair amount of experience to make this judgment.

Basically I'm wondering if in this dark brown state the LSD is fit for consumption, and for an explanation of what has happened to it chemically.

Cheers

(The above is an x-post from the Psychedelic Drug Discussion forum)
 
Activation of serotonin receptors in the periphery causes vasoconstriction.. that is why it was called serotonin in the first place (sero=blood, tonin=increasing vascular tone). It is stored in platelets, in order to cause vasoconstriction at places of injury, to decrease blood loss. Obviously, certain subclasses of the receptor cause the vasoconstriction, and evidently BromoDragonFly is a particularly potent agonist of these receptors.
 
melange said:
the bromo-dfly wikipedia states:

"Also, a Swedish man had to have the front part of his feet and several fingers on one hand amputated after taking a massive overdose. Apparently the compound acted as a long-acting efficacious vasoconstrictor, leading to necrosis and gangrene which was delayed by several weeks after the overdose occurred. Several other cases have also been reported of severe peripheral vasoconstriction following overdose with Bromo-DragonFLY, and a similar case is also known from DOB"



is this true?



and why?
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Yes it is true but it is unclear why exactly.

Bromo-dragonfly is a very potent 5HT2B agonist which is a receptor that causes vasoconstriction, and it is also suspected that some 5HT2A agonist hallucinogens may also be alpha-1 adrenergic agonists given the structural similarity with selective alpha-1 agonists like methoxamine (2,5-dimethoxy-beta-hydroxyamphetamine).

Since alpha-1 agonists are also vasoconstrictors, it seems likely that bromo-dragonfly (and also DOB etc) may cause vasoconstriction via two seperate mechanisms that will be synergistic, so its not surprising the effect can be quite pronounced at high doses.
 
vortex30 said:
Explain how Nitrous Oxide is a NMDA antagonist.
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Open channel blocker, binds in the middle of the pore that usually lets Ca2+ ions through.

Does N2O affect any other receptors/neurotransmitters in the brain?
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Not directly but NMDA antagonist effect leads to multiple downstream effects.

How is N2O metabolized?
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Pretty sure its excreted unchanged but not sure on this.

Is there a dangerous number of 8g chargers not to go over in a single dose? I've done 3 at the most, but was thinking I may want to try 4. Essentially, what is the LD50?
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The main risk is suffocating from not breathing enough air. N2O is not a strong enough anesthetic agent to produce fatal respiratory depression before it wears off, so fatalities invariably result from people passing out while breathing the pure gas. However regular heavy use of N2O can deplete vitamin B12 which can lead to nerve damage if not treated.

Can you be allergic to N2O?
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Yes you can be allergic to just about anything so I doubt N2O is any exception.
 
Can chronic use of MAO-B inhibitors result in the upregulation of the transcription of this enzyme. I did a google search and found of course that its transcription can be upregulated, I just don't know whether selegiline or rasagiline will do that.
 
I believe the term is amateur 'bioassay'.

I am aware of the subjective feelings of MAO B inhibition and of those of MAO A inhibition; I have been on selective inhibitors for both of the isoforms. As such, when the effect of selegiline decreased (yes, obviously, partially due to Dopamine receptor downregulation,) I increased the dose daily until virtually the same effects as original were reached. At one point I raised the dose too high and could feel the effects of inhibition of MAO A start to creep in (rumbling gut, diarrhoea) etc.
 
No one would answer this in OD:

"Lets say that you have two hypothetical drugs, each inducing the same degree of monoamine release IN SUM. However, drug 1 releases a moderate amount of dopamine, a large amount of 5ht, and a moderate amount of NE, while drug 2 releases a large amount of dopamine, a moderate amount of 5ht, and a moderate amount of NE. Their durations are identical, as are the levels of compulsion to re-dose, as are the toxcicities of the metabolites.

Which would be more neurotoxic? What is the bottleneck in the pathological uptake of DA by SERT, the amount of intercellular dopamine or the number of SERT that have 'spat out' serotonin, leaving them open to reuptake of dopamine?

ebola"
 
A greater amount of dopamine/norepinephrine release along with moderate serotonin release is probably worse (eg methamphetamine, which is much more toxic than MDMA).

The uptake of DA by SERT is kind of hard to characterize:
Temperature and 3,4-methylenedioxymethamphetamine alter human serotonin transporter-mediated dopamine uptake

Shannon N. Saldaña and Eric L. Barker

Although studies have suggested that dopamine can be transported by serotonin transporters (SERTs), such activity has not been characterized at the cloned SERTs. Dopamine and serotonin uptake by human SERT expressed in HEK-293 cells was compared at 37 and 40 °C. Elevated temperature was found to alter serotonin transport, but had no significant effect on dopamine transport. These effects led to a 10-fold increase in the serotonin:dopamine transport ratio reflecting an increased preference of SERTs for dopamine as opposed to serotonin at the higher temperature. The effects of 3,4-methylenedioxymethamphetamine (MDMA) on SERT-mediated dopamine transport were also evaluated by pre-incubating SERT-expressing cells with MDMA. The presence of intracellular MDMA caused a decrease in [3H]dopamine uptake but had no effect on [3H]serotonin transport suggesting that intracellular MDMA may be capable of inhibiting transporter function.
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I'm guessing for acute neurotoxicity like that of methamphetamine you need elevated temperatures from 5HT release and a large amount of DA and NE release. I'm not sure the intracellular concentration of 5HT had much to do with it.
 
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permastoned said:
Doesn't it also have a lot to do with the specific metabolites of the drug?
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I don't think so. The main metabolites are p-OH-METH, p-AMP and p-OH-AMP. The hydroxylations I believe are mediated by hepatic P450 enzymes. The effect on catecholamines and serotonin (high amounts of radicals generated by MAO degredation under elevated temperatures destroying mitochondrial DNA and forming toxic metabolites of the endogenous neurotransmitters) is probably more responsible for the neurotoxic effect. I'd be willing to bet that any potent releaser of all three monoamines may cause neurotoxicity.
 
I don't think so. The main metabolites are p-OH-METH, p-AMP and p-OH-AMP. The hydroxylations I believe are mediated by hepatic P450 enzymes. The effect on catecholamines and serotonin (high amounts of radicals generated by MAO degredation under elevated temperatures destroying mitochondrial DNA and forming toxic metabolites of the endogenous neurotransmitters) is probably more responsible for the neurotoxic effect. I'd be willing to bet that any potent releaser of all three monoamines may cause neurotoxicity.
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I'm fairly sure that this isn't the case. Some releasers, for example the aminoindans show promise with their lacking neurotoxicities:

Re http://en.wikipedia.org/wiki/Indanylamphetamine

This indanylamphetamine, (also called IAP, 1-(5-Indanyl)-2-aminopropane or 5-(2-aminopropyl)indane) is an analog of MDA, but with both oxygens in the methylenedioxy bridge replaced by methylene (CH2) units. It has been shown to not be a serotonergic neurotoxin, and is active at 0.2 mg/kg in Nichols' lab rat tests, compared to 0.8 mg/kg for MBDB. However, the lab rat results show that the effects should be somewhere inbetween MDA and MBDB, as it doesn't fully substitute for the purely serotonergic compound MMA (3-Methoxy-4-Methyl- Amphetamine), but does share some of the dopaminergic effects of MDA. Further animal tests showed that IAP does not substitute for amphetamine, so the compound is not a particular stimulant either. IAP is also one of the most active serotonin-releasing agents known so far, together with the 4-iodoamphetamine and 4-methylthioamphetamine (4-MTA). However, 4-iodoamphetamine is a serotonergic neurotoxin, and 4-methylthioamphetamine has also shown signs of toxicity, as it also exhibit MAOI properties. This together with is serotonin-releasing properties, makes it prone to give a serotonin syndrome in people taking it, and several 4-MTA related deaths has been reported. The same cannot be ruled out for IAP, so caution is advised in any human testing of this compound. The animal test results suggest that the active dose is somewhere between 20-40mg. In October 1998, there were news reports that the compound had been seized together with other ecstasy-like compounds in South Australia (possibly Adelaide), confirming that it has been manufactured in clandestine laboratories there.
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Or the closely related napthylamphetamine, http://en.wikipedia.org/wiki/Naphthylaminopropane.

Naphthylisopropylamine (PAL-287), or naphthylaminopropane (NAP), is a psychoactive drug and research chemical currently under development for the treatment of alcohol and stimulant drug addiction. It functions as a non-neurotoxic and well-proportioned serotonin, norepinephrine, and dopamine releasing agent.[1]
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If I recall right IAP is not strongly catecholamine releasing.

Monoamine oxidase inhibitors are well known to be preventative in neurotoxicity due to their ability to inhibitor production of hydrogen peroxide, so 4-MTA doesn't count.

If that naphthylisopropylamine compound binds with high affinity for the 5HT transporter and with strong competition, it may prevent the reuptake of amines into the neuron and in doing so their deamination by MAO. Notice METH and MDMA release 5HT at far lower concentrations than they bind to SERT. My guess is that's the case given the structure of 5HT and the naphthyl substituent being closer to it in terms of size than the phenyl substituent. This could be the case with IAP as well. It could also be a 5HT2A antagonist and prevent neurotoxicity via that route as well.

But that naphthyl group may prove carcinogenic yet, so I'd be cautious.

Edit: This paper is kind of dubious too (naphthylisopropylamine):
"Increasing evidence indicates that SERT sites are involved
in the mechanism by which fenfl uramine increases the risk
of developing PPH (for review, see Rothman and Baumann
71 and references therein). For example, medications that
increase the risk for PPH have in common the ability to
release 5-HT by a SERT-mediated process. On the other
hand, not all 5-HT releasers are associated with PPH. The
antidepressant trazodone is not associated with PPH, yet its
major metabolite, mCPP, is a potent SERT substrate, as
noted above. 2 Experimental data from a mouse model of
hypoxic pulmonary hypertension suggest that 5-HT 2B recep-
tors may also contribute to the pathogenesis of PPH. 77 The
relevance of these fi ndings to drug-induced PPH is not clear,
since aminorex, a 5-HT releaser that caused an epidemic of
PPH in the 1960s, 78 has minimal activity at 5-HT 2B recep-
tors. Viewed collectively, the available data suggest that it
should be possible to develop dual DA/5-HT releasers
devoid of fenfl uramine-like adverse effects. In particular,
we have suggested that a lead drug molecule should be
chemically distinct from the phenylethylamine structure
shared by amphetamine-like agents and should lack signifi -
cant agonist activity at 5-HT 2B receptors. 79"

Great, it's too bad they didn't bother going through the literature to find out mCPP is also a 5HT2B antagonist.

Aminorex is a 5HT releaser and 5HT is well known to cause PPH. What's their point?

"Viewed collectively, the available data suggest that it
should be possible to develop dual DA/5-HT releasers
devoid of fenfluramine-like adverse effects."

Not really, at least not from any of the data you provided.

Aside from that, "The data in Figure 7 show that PAL-287 does not support self-administration
behavior." Doesn't sound like it's much fun.
 
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