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Comment · Tue, September 17, 2024 · Natrium Health & Nootropics Depot

A Potential New Nootropic (SYNTHESISED AND TRIED) results

Original post in this thread

cmnews08 · 339 points

If you didn't see the original, take a look here

Anyways, to start let me post the synthesis.

Piperidinil synthesis

I chose to not include the dichloro aspect of the original post as I knew it would cause serotonin interactions and that's where the potential harm could be, I didn't want to create a serotonin reuptake inhibitor which is what I theorised the dichloro would cause.

Let me say, this synthesis took a lot of money, time and effort before I got a good yield. I am working on a more cost and time effective synthesis.

I synthesised this from a base chemical, Phenyl(piperidin-2-yl)methanol, which is pricey at about $200 (£152.38) a gram. Leaving little room for error.

Reacting this with thiourea and Chloroethane gave an intermediate with deaminated to a product that could be reacted carefully with Sulfuryl chloride, Ammonia and Hydrogen peroxide would give the chemical I wanted.

I failed 5 times before I got it right, costing me close to $700 (£530), however I finally…

What they were answering

cmnews08 · 3 points

It does seem the effects of modafinil are not tied to or symptomatic of any traditional CNS stimulants or nootropics. Its exciting to think the positives of modafinil don't disappear if you use a methylphenidate or potentially amphetamine base as a sort of "carrying" group.

In short my takeaway is mainly that modafinil isn't a variation on any traditional CNS subtances but a whole other being that can be altered with aspects of CNS substances to blend both worlds.

This is hypothesis though.

u/MisterYouAreSoDumb · Natrium Health & Nootropics Depot

I agree. There is a novel mechanism under the hood of the afinils that we don't yet fully understand. Years back when we were doing all our synthetic research, my theory was that it was mediated by one of the 5-HT sub-receptors. That's one thing that led me to 9-Fluorenol, which I coined the name Hydrafinil for. People gave me shit here on Reddit for that name, but studies are actually using it now!

Mass spectrometric characterization of urinary hydrafinil metabolites for routine doping control purposes

Anyway, that 5-HT sub-receptor affinity is still unproven with Hydrafinil. However, there is a 1996 study showing that 5-HT3 is at least part of how modafinil affects GABA levels.

The vigilance promoting drug modafinil decreases GABA release in the medial preoptic area and in the posterior hypothalamus of the awake rat: possible involvement of the serotonergic 5-HT3 receptor

It was also discussed in the below literature review.

Mechanisms of modafinil: A review of current research

Modafinil also causes an increase in serotonin, but not by inhibiting uptake or release. I believe the current theory is that is not a direct mechanism, but is due to increases in the glutamate–glutamine pool, possibly as a result of increased glutamine synthetase activity. There are 5-HT-glutamate co-releasing neurons that are affected by chronic stress. Modafinil might be resulting in increases in 5-HT through those neurons.

Modafinil: A Review of Neurochemical Actions and Effects on Cognition

The modafinil's involvement in the orexin system is curious. It doesn't seem to bind directly, but orexin is playing a role somehow.

Modafinil more effectively induces wakefulness in orexin-null mice than in wild-type littermates

Modafinil and orexin system: interactions and medico-legal considerations

Serotonin is known to hyperpolarize orexin neurons through the 5-HT1A receptor.

Serotonergic regulation of the orexin/hypocretin neurons through the 5-HT1A receptor

Then you get to histamine. Modafinil increases histamine levels, but not by a direct mechanism. The current theory is the reduction in GABA causes it, which then attenuates the inhibitory function GABA has on the histaminergic system. So it is a complex mechanism with a lot of downstream effects, for sure. Making modifications to the molecule to increase the DA and NE effects, like your piperidine modification, can make a pretty interesting feeling compound.

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