10-Methoxy-Harmalan - liquid product for R&D

[Riesensackteil]

Does it feel like something you'd take in the morning or at night?

Fourtillan calls it Waking Hormone and Valentonine the real sleep hormone

 

[Mauritio]

I am so excited to try this myself It sounds like that pill from the movie Limitless
How does it compare to lisuride and metergoline? I usually get nausea/fuzzy sensation from both, any sides like this from 10MH? Also any social skills improvement from this?

I wouldn't compare it to that
Feels a lot closer to lisuride than metergoline IMO. But I didn't particularly like metergoline. So that's a plus for me. It feels more relaxing than lisuride.

No side effects so far .

I hadn't had much social interaction so far, but I feel like I'm less self-conscious and more relaxed.

 

[Mauritio]

Does it feel like something you'd take in the morning or at night?

So far I'd say both, but it's too early to tell. Doesn't feel very stimulating.

 

[conrad0602]

I've taken 2 drops orally 3 X a day for two days. I have experienced moments of increased motivation and positivity on both days albeit short lived. I took last dose before bed yesterday and didn't sleep for ages but I can't say for sure that this was the 10 MH. Going to take a before bed dose again tonight and see if I still have trouble sleeping.

 

[Epik]

Fourtillan calls it Waking Hormone and Valentonine the real sleep hormone

Just watched the interview. Probably gonna use it in the morning with food, apparently it can increase cortisol

 

[Charger]

Is there any risk of serotonin rebound from something like this? I do still get mild relaxation but I'm also noticing more serotonin symptoms throughout the day outside of dosing in the form of aggression, irritability, and ruminating more.

There's other variables that could be contributing but I was also thinking that it could be 5ht1a antagonism or mao-a inhibition.

 

[tankasnowgod]

So far I'd say both, but it's too early to tell. Doesn't feel very stimulating.

It might depend, but I often find things that lower or antagonize serotonin to be somewhat stimulating. After I got used to cypro, I couldn't take it too close to bed, as I would often find myself a bit too wired to sleep (if wired is the right word). I could still take it in the evenings, say with dinner, but I think the serotonin antagonism eventually made up for any anti-histamine drowsiness.

 

[Soren]

Anyone know if there is any negative or potential for negative interaction between 10 Methyoxy and non-ergot dopamine agonists such as Rotigotine?

As far as I can tell Rotigotine along with being an agonist of all the dopamine receptors it is also a partial 5HT1A agonist. Don't know if this is an issue.

" It is also an antagonist at α-2-adrenergic receptors and an agonist at the 5HT1A receptors. Rotigotine also inhibits dopamine uptake and prolactin secretion. "

PubChem Rotigotine (Compound)

I've combined Rotigotine with metergoline and not had any issues so I would assume it would be no different here.

 

[Mauritio]

Do you have any sources for 10MH specifically beeing a 5ht1a antagonist?
It's indeed an interesting receptor .Some cool molecules like CBG or lisuride are an agonist on that receptor .

I have to correct myself. CBG is an ANTagonist on 5HT1A... just so I dont make this even more confusing than it already is
So 10MH might help with premature ejaculation ...

It might depend, but I often find things that lower or antagonize serotonin to be somewhat stimulating. After I got used to cypro, I couldn't take it too close to bed, as I would often find myself a bit too wired to sleep (if wired is the right word). I could still take it in the evenings, say with dinner, but I think the serotonin antagonism eventually made up for any anti-histamine drowsiness.

Sure. Decreasing serotonin increases dopamine. So that alone might make it stimulating. And as haidut said there might even be direct D2 agonism . Although D2 agonists like bromocriptine or phenylpiracetam have a certain feeling to them. And 10MH does not have that (so far).
It actually feels more GABAergic than dopaminergic.

My experience was just based on 1 drop, so there might be intra- and interindividual differences down the line.

 

[Mauritio]

1. Judging from the closely related chemical below, it seems there is antagonism on 5-HT1 and 5-HT2, with possible agonism on D2.

6-MeO-THH - Wikipedia

en.wikipedia.org

"...Studies in rats have shown it to bind to a number of serotonin 5-HT1 receptors and 5-HT2 receptors, dopamine D2 receptors, benzodiazepine receptors, and imidazoline receptors.[2][3][4]"

2. I don't find it to have MAO-A inhibiting effects. Some of the studies I saw on beta-carbolines concluded that if there is any MAO inhibition it is more likely on MAO-B instead of MAO-A.

I looked at the second cited study from wikipedia and they say :
"The beta-carbolines were found to bind with modest affinity at 5-HT(2A) receptors, and affinity was highly dependent upon the presence of ring substituents and ring saturation. The beta-carbolines displayed little to no affinity for 5-HT(1A) serotonin receptors, dopamine D(2) receptors and, with the exception of beta-CCM, for benzodiazepine receptors."

If you look at the corresponding table and data specifically for 6methoxyharmalan you can see that it has the highest affinity for 5HT2c followed by 5HT2a ,but affinities are so low that I'd say I doesn't do much at any of those 2 receptors.
The picture is even clearer for D2, GABA-A and 5HT1a there's almost no affinity at all for those receptors !

(Binding of beta-carbolines and related agents at serotonin (5-HT(2) and 5-HT(1A)), dopamine (D(2)) and benzodiazepine receptors - PubMed)

 

[Mauritio]

Those 2 studies mention beta carbolines affecting the Imidazoline receptors.
They dont mention 6methoxyharmalan specifically ,but harmalan itself has decent affinity for I1 and especially I2 .

beta-carboline binding to imidazoline receptors - PubMed

A series of beta-carbolines were prepared and their affinities for imidazoline (I(1) and I(2)) sites evaluated. Selected compounds were also examined at alpha(2)-adrenoceptors. Some of the beta-carbolines were found to bind with high affinity to I(2)-sites and this affinity was dependent on both...

pubmed.ncbi.nlm.nih.gov

Binding of beta-carbolines at imidazoline I2 receptors: a structure-affinity investigation - PubMed

A series of ring-substituted (i.e., methoxy and bromo) 3,4-dihydro- and 1,2,3,4-tetrahydro-beta-carbolines was examined at I(2) imidazoline receptors, as was the effect of ring-opening, ring-expansion, and translocation of the piperidinyl nitrogen atom. Several analogues were identified that...

pubmed.ncbi.nlm.nih.gov

Imidazoline receptor - Wikipedia

en.m.wikipedia.org

 

[Lokzo]

I am enjoying reading everyone’s experiences in this thread. Keep it going!

My 10-MEO-H arrived yesterday.

Very excited to trial it as a Cyproheptadine alternative to truly see if this gives the same rebound effect that reverses PSSD.

 

[Wagner83]

An article of the infamous Fourtillan discussing the product among other ones.

 

[haidut]

I looked at the second cited study from wikipedia and they say :
"The beta-carbolines were found to bind with modest affinity at 5-HT(2A) receptors, and affinity was highly dependent upon the presence of ring substituents and ring saturation. The beta-carbolines displayed little to no affinity for 5-HT(1A) serotonin receptors, dopamine D(2) receptors and, with the exception of beta-CCM, for benzodiazepine receptors."

If you look at the corresponding table and data specifically for 6methoxyharmalan you can see that it has the highest affinity for 5HT2c followed by 5HT2a ,but affinities are so low that I'd say I doesn't do much at any of those 2 receptors.
The picture is even clearer for D2, GABA-A and 5HT1a there's almost no affinity at all for those receptors !

View attachment 30009
(Binding of beta-carbolines and related agents at serotonin (5-HT(2) and 5-HT(1A)), dopamine (D(2)) and benzodiazepine receptors - PubMed)

Those studies are just receptor binding, which is very tricky to do and notoriously unreliable to calculate. The original study from the 1960s had an in-vivo component, which showed strong anti-serotonin effect. My guess is that the chemical may be a TPH inhibitor or potentially antagonist on 5-HT3 given its structural similarity to ondansetron.

Ondansetron - Wikipedia

en.wikipedia.org

 

[Mauritio]

Those studies are just receptor binding, which is very tricky to do and notoriously unreliable to calculate. The original study from the 1960s had an in-vivo component, which showed strong anti-serotonin effect. My guess is that the chemical may be a TPH inhibitor or potentially antagonist on 5-HT3 given its structural similarity to ondansetron.

https://en.wikipedia.org/wiki/Ondansetron[

Okay.

There's a good chance it works on the imidazoline receptors, especially I2 seems likely . What do you think about that?

 

[Lokzo]

Any further updates/experiences?

I’m planning on trialling in the next couple of weeks.

 

[conrad0602]

Any further updates/experiences?

I’m planning on trialling in the next couple of weeks.

Waiting to see how it effects the rest of us ?

 

[haidut]

Okay.

There's a good chance it works on the imidazoline receptors, especially I2 seems likely . What do you think about that?

Yep, that is likely, based on another study I saw, and I think that study said the chemical may work similarly to clonidine.

 

[llian]

Yep, that is likely, based on another study I saw, and I think that study said the chemical may work similarly to clonidine.

10MH really is a TPH inhibitor ? This means that it can potentially shut down all serotonin receptors ?
Also what dr. Peat thinks about this substance?

 

[haidut]

10MH really is a TPH inhibitor ? This means that it can potentially shut down all serotonin receptors ?
Also what dr. Peat thinks about this substance?

I never said it is a TPH inhibitor. It is just a guess, not a claim, since it did display anti-serotonin effects in-vivo. If its affinity for 5-HT2 receptors is reported as weak, then TPH inhibition and/or 5-HT antagonism (given the structural similarity with ondansetron) may explain the in-vivo effects.
I don't know what Peat thinks of it, have not asked him, and in fact stopped asking him about ~4 years ago due to people using his comments he made to me in emails to claim I am using his name to sell products. So, if somebody wants to ask him that's fine, but I am not getting him involved any more in regards to our products.