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

[dread]

When they say that Fencamfamine is a partial DA releaser and a partial DRI, how exactly does that work? Does it reverse some DAT:s and inhibit others? Or does it bind to the DAT and then only reverse it occasionally? Or is there some completely different mechanism?

Wiki says it releases DA by the same mechanism as amphetamine, but does not say what mechanism it uses to inhibit the reuptake.

So anyone got an answer for this?

 

[surrеalist]

Yeah, that is strange. I was under the impression that a DAT inhibitor bends the transporter so that neurotransmitters can't be pumped out of the synapse, and DA releasers bend and make some "channel" in the transporter that allows dopamine to flow into the synapse from presynaptic vesicles, with the concentration of dopamine trying to reach an equilibrium. This is opposed to normal DAT function which pumps against the concentration gradient.

I bet this is an example of multiple binding sites on DAT- fencamfamine must have affinity to both the phenethylamine DAT-phosphorylating site and to somewhere else, the phenyltropane site perhaps.

I'm not saying that these compounds overlay, cuz I haven't done the comparison. However, they're pretty close. First, remember that 5-MeO-DMT has a greater affinity in general for the serotonin receptors than does 4-MeO-DMT. So, the methoxy in the ORG compound and the methoxy group meta to the bromine in your proposed compound would overlay the methoxy in 5-MeO-DMT. Then the amine (I'd propose making it a secondary or tertiary amine) in your compound would overlay somewhat closely with the amine in the ORG compound and the tryptamines.

Thanks, I'm still preplexed over several things, and it sucks that things aren't as consistent as I thought. I was thinking that the more selective 5-HT2A agonists make for better drugs, but who knows. LSD has nearly equal 5-HT2C affinity as 5-HT2A. I think it's even an antagonist at some.

Here's a poor sketch. Black is 5-methoxy-4-hydroxy-DMT, red is the compound I suggested, and blue is the ORG compound. You might be right that the red compound will behave better as a secondary or tertiary amine, but I'm a bit skeptical because for some reason that kills activity in phenethylamines. Putting the equivalent of an a-methyl group is probably acceptable.

 

[Enkidu]

Well, I haven't seen any papers on the theory behind the development of the ORG compound. However, since the ORG compound is a secondary amine, we should surmise that, if it had to bind in either the tryptamine orientation or the phenethylamine orientation, we should choose the tryptamine orientation.

The current opinion (as far as I can tell) is that the 5-MeO in 5-MeO-DMT does not overlay the 2-MeO in phenethylamines.

Is that drawing a 3D energy minimized conformation comparison? It doesn't look like it.

 

[seep]

Is that drawing a 3D energy minimized conformation comparison? It doesn't look like it.

Blue's methoxy has a steric effect on its pyrrolidine, as does the saturated portion of the indane.

 

[hamhurricane]

quick question about agranulocytosis (specifically levamisole induced)

are existing agranulocytes destroyed, or is it only the formation of new cells which is inhibited? if one uses contaminated cocaine (or aET for that mater) can a single administration produce dangerous results or is it a cumulative effect that requires repeated administration? also how long do the effects last after a single admin. of an agranulocytosis causing drug, eg if one waits a week is that enough time to let the cells regenerate?

 

[Hammilton]

Well, I haven't seen any papers on the theory behind the development of the ORG compound. However, since the ORG compound is a secondary amine, we should surmise that, if it had to bind in either the tryptamine orientation or the phenethylamine orientation, we should choose the tryptamine orientation.

The current opinion (as far as I can tell) is that the 5-MeO in 5-MeO-DMT does not overlay the 2-MeO in phenethylamines.

Is that drawing a 3D energy minimized conformation comparison? It doesn't look like it.

I don't think it was either. doesn't seem available now.

Anyway, I've always thought that the ergolines would bind more similarly to phenethylamines. But unfortunately what people think has generally been found to be wrong.

Anyway, I'm wondering if anyone is aware of analogues of benzodifuran w/ the oxygen replaced by NH? It could still accept a H-bond (though as I understand a secondary amine forms much weaker H-bonds, correct?). Thiophene and furan analogues of indoles are active, if less potent. What about of the dragonflys though? I have a feeling it's been done, but I don't remember seeing it.

 

[dread]

I have a feeling it's been done, but I don't remember seeing it.

I also have similar feeling. I seem to remember someone talking about a dragonfly derivative where one of the furans was changed to a pyrrole, but I'm not sure if that was more chemical masturbation or a reference to an actual chemical.

 

[opiaddict]

meth symthesis

I recall our oragnic chemistry teacher showing us the synthesis of methamphetamine. Not that I would try, but curious from a biochemical point of view my question is this: why can't you use ephedrine as a starting product and do a reduction on the =0 by usimg a strong reducing agent like Kmno3/LiAl hydride? It made sense when I drew it out, and then I think there may be just a methyl group to add. I don't know. Why is the process such an endothermically contained reaction? I mean, why can't you by pass all these steps and do an addition rx + a reduction?

 

[opiaddict]

I am sorry I meant KMNO4 as a reducer.Or am I off base here?

 

[N0 W4RN1NG]

I am sorry I meant KMNO4 as a reducer.Or am I off base here?

For starters, KMNO4 is a strong oxidizer, you're not going to get methAMP as a result...

 

[dread]

For another thing, there's no ketone on ephedrine, only a beta-hydroxyl. And another thing, no fucking synth discussion.

 

[Metcalf]

MDA-NBOMe

I'm not too pharmacologically savvy. Is this compound potentially active? (in the vein of 2CB-NBOMe)

 

[nuke]

I'm not too pharmacologically savvy. Is this compound potentially active? (in the vein of 2CB-NBOMe)

I doubt it, as I recall the amphetamine derivatives in that paper lost their affinity for 5HT2 receptors.

 

[Alotsa]

Turning hearoin into a less potent product?

There is a lot of information and theories out to make heroin from lesser opiates.

But what if you wanted to Take Heroin and make it less potent?

Is this possible to break down heroin into a less extreme drug more like pod tea. methadone, Oxycontin, or even hydrocoden? possiablr dilute it enough for oral ROA? something?

Why would i ask such a question? well I don't want something as strong as heroin and It's very hard to find pills for me and when i do they are quite expensive. I think a lot of people who are heroin addicts could had avoided that if it wasn't so much cheaper than pills ( though i cant say from experience).

Any one elase though of this? Is there any information on a process to do this? And Has any one successfully done this?

I live on the west coast and imagine the only herion i could optain would be that of the black tar verity.

 

[nuke]

You can eat heroin, it's just not very bioavailable (~30-40% IIRC). If you expose it to either an acid or base it breaks down into acetic acid and morphine.

Once you stop doing lots of morphine/heroin you're going to find yourself not wanting to make it any less strong really quickly.

Anyway, no synthesis discussion.

 

[any major dude]

I doubt it, as I recall the amphetamine derivatives in that paper lost their affinity for 5HT2 receptors.

Is MDA's activity mediated by 5ht2 receptor subtypes? I recall it having affinity for 2b, but not much for 2a or 2c, IIRC.

 

[/navarone/]

Treating your heroin with sodium hydroxide (or mybe even concentrated baking soda) will yield up in morpine and sodium acetate.

Then you can turn it into another esterified opioid with a lil chem knowlegle

 

[/navarone/]

It's metabolised by MAO very rapidly, for one. For two, I don't believe it has enough (any?) 5HT2a affinity. I'm having trouble

I guess you forgot to mention that even DMT is completely metabolized by MAO (in the digestive track i think)
Hence why DMT is smoked in pipes or sometimes idiotically insufflated since i heard reports that its burns like f**k and tastes like s**t when it drops down the mouth.
MMT (monometyl T) is also a mild psychedelic but far from DMT and it will also get annihilated by MAOa.

However it seems that bufotenin and 5-MeO-DMt doesn't get attackes as much by MAO.
In fact 5-Meo-DMT is active orally at 30mg and up to 2 milligrams when inhaled/injected (unlike DMT which is active at a dose of 15-30mg when inhaled).

That's the reason why the DMT containing Ayahuasca infusion drinks, (a very popular 'tea' in some parts of South America), is orally active.
Magic? No, its due to the presence of MAO harmala alkaloids in their infusion.

Also I think that the heavily methylated amine changes the polarity of the amine (increasing structure and lipophilicity) and thus increasing the psychedelic effect and 2-HT2a receptor affinity.
I, wihout reference unfortunately, can somehow relate that to the differences d-amphetamine, d-methamphetamine and d-dimethylamphetamine.
_______________________

BTW i found this on wiki:

The bio syntheis of endogenous DMT

Dimethyltryptamine is an indole-alkaloid derived from the shikimate pathway. Its biosynthesis is relatively simple and summarized in the picture to the left. In plants, the tryptophan is produced endogenously where in animals the tryptophan used comes from diet. No matter the source of tryptophan, the biosynthesis begins with the decarboxylation of L-tryptophan (1). Once decarboxylated, tryptamine (2) is dimethylated by S-adenosyl-methionine (SAM) via nucleophilic attack. This reaction is mediated by tryptamine-N-methyltransferase enzyme. This produces the product (3). The mechanism has been proven by radio labelling of SAM with carbon-14. The study found that various mammal tissues contained enzymes capable of performing the above transformation.

EDIT:
It would be fun coming up with a drug that enhanced SAM, That would make you dream like fuck since ,FWIH, DMT plays a big role in dreaming.

 

[MurphyClox]

EDIT:
It would be fun coming up with a drug that enhanced SAM, That would make you dream like fuck since ,FWIH, DMT plays a big role in dreaming.

Considering the large number of biological reactions that are performed with the aid of SAM, this suggestion is just pointless.

 

[hamhurricane]

Disposal of JWH-xxx in the UK

correct me if im wrong, but the scheduling of the JWH and CP series chems in the UK seemed to happen around xmas with no prior government warning. im sure we all noticed how overnight the cannabinoids in question disappeared from vendor menu's but my question is this - if the scheduling did appear without warning how can vendors be expected to dispose of their stock before its too late? if there was warning is their some official protocol for disposal of chems which are on the verge of scheduling - simple toilet flush?

if thats the case i wouldn't be surprised if the english waste treatment facilities were encountering floes of JWH-018.