Vinero

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How does this compare to Memantine dosage wise? Let's say we have 40 mg of Memantine, is this equal in strength to 40 mg of Adamantane??
 

satsumass

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I'll check it out. However if that kind of inner ear dysfunction disrupts balance it's probably not my issue - my balance is quite good. That said, I have a friend who had life-changing results from a frenectomy - fixing a "tongue tie". Apparently if even a minor tongue tie is untreated it can have huge repercussions with everything from balance to social behavior. I'm mentioning that because, seemingly unimportant issues (like inner ear stuff) can have significant compounded impacts into adulthood.

To what did he attribute the cause of the positive effects of the frenectomy? I had a slight-moderate tongue tie and also got that procedure with the hope that it helps with my sleep apnea which is already partially treated...haven't seen anything "life changing" though
 

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Awesome, thanks! It would be nice if he does a newsletter or a radio show on adamantane and its derivatives. I think there are one of the most versatile substance in our possession as they oppose most of the mediators of the stress reaction he has been writing about - cortisol, prolactin, serotonin, acetylcholine, glutamate, viruses, bacteria, etc.
In the latest KMUD interview (KMUD: 3-17-17 Endocrinology (Part 1): Parkinson's) at the 38 minute mark, Ray talks about Memantine and Amantadine in the context of an alternative treatment for Parkinson's rather than dompamine drugs or L-Dopa which have detrimental side effects long term. He said Memantine and Amantadine are beneficial for their anti-excitatory effects on the cholinergic and glutamatergic systems. He also said they lower exposure to nitric oxide (NO) because the glutamate system ends up producing NO which suppresses mitochondrial respiration and energy production. He concludes that Memantine and Amantadine are restoring the energy process by reducing the effects of stress in a systematic way.
 

Jsaute21

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Thanks @Mito, that is a helpful tidbit. @haidut and others, since Diamant is particularly beneficial from a neuro standpoint, wouldn't it make sense to directly apply to our Rat's forehead?
 

Pointless

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OK so I tried this on a mammalian subject. 20 drops last night, sublingual and then swallowed. Not much was reported except for a minty taste.

The next morning another 20 drops were tried, with the intention of doing 20 drops each morning from then out. Lots of adrenaline with body rushes and loose stools. A lot of salt, sugar, and water calmed that down. But soon after the subject started to notice incredible energy. There was a very strong desire to work out, like never before. There was some manual labor at work, and his endurance was way up, though he did get out of breath.

Still an early report, but the subject is going to do a much lower dose next time (maybe 1 drop) and work on bag breathing and increased salt consumption before getting back up to a dose that might replace Cyproheptadine or some of the other supplements he's taking.
 

DKayJoe

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Does anyone think this would pair with cypro well for reducing stress as well as pushing up dopamine? Been having great success with cypro but it leaves me feeling a little flat at times which I attribute to dopamine levels being low.
 
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Can you show me specifically where in, for example, the study on HDAC inhibition (doi: 10.1016/j.bmcl.2013.03.002) the HDAC inhibition activity of unsubstituted adamantane (C10H16) is compared to the HDAC inhibition activity of substituted derivatives of adamantane?

Yes, here it is. Not only was adamantane extremely potent HDAC inhibitor by itself but messing with its structure reduced that activity and its anti-cancer effects.
"...Initially we started our SAR studies with unsubstituted adamantane, (compound 5) which shows the HDAC inhibitory activity about 70 nM with 0.5-2.8 µM range of anti-cancer activity. Replacing hydrogen in 3rd position of 5 with ethoxy, methoxy, hydroxyl, phenyl and hydroxymethyl (compounds 6, 7, 8, 9 & 10), decreased the potency against HDAC as compared to 5 by 3 fold and the anti-cancer activity also reduced."
 
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haidut

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How does this compare to Memantine dosage wise? Let's say we have 40 mg of Memantine, is this equal in strength to 40 mg of Adamantane??

As I mentioned in another post, I made it so that the amount of adamantane per unit is about the same as the one for memantine. A common dose of memantine is about 30mg daily. The 40mg and higher doses I think are used mostly for Parkinson since the dopaminergic effects become very pronounced with higher doses.
 
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@haidut yes some guidelines for memantine use vis a vis Adamantane use would be helpful

As I mentioned above, they should have similar effects in about the same doses. A common dose of memantine is about 30mg daily.
 
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In the latest KMUD interview (KMUD: 3-17-17 Endocrinology (Part 1): Parkinson's) at the 38 minute mark, Ray talks about Memantine and Amantadine in the context of an alternative treatment for Parkinson's rather than dompamine drugs or L-Dopa which have detrimental side effects long term. He said Memantine and Amantadine are beneficial for their anti-excitatory effects on the cholinergic and glutamatergic systems. He also said they lower exposure to nitric oxide (NO) because the glutamate system ends up producing NO which suppresses mitochondrial respiration and energy production. He concludes that Memantine and Amantadine are restoring the energy process by reducing the effects of stress in a systematic way.

Thanks. I would also add that camphor has very similar properties and in fact all adamantane derivatives have strong camphor smell, which shows how closely related they are in terms of effects. I think Peat said something similar in regards to that quantum theory of smell by Luca Turin - i.e. similarly acting substances are perceived as having a similar smell.
 
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Thanks @Mito, that is a helpful tidbit. @haidut and others, since Diamant is particularly beneficial from a neuro standpoint, wouldn't it make sense to directly apply to our Rat's forehead?

Yes, it may be a good approach. I have tried the neck as the blood vessels there go directly into the brain, but above eyebrows is apparently another area that would result in higher brain distribution.
 
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OK so I tried this on a mammalian subject. 20 drops last night, sublingual and then swallowed. Not much was reported except for a minty taste.

The next morning another 20 drops were tried, with the intention of doing 20 drops each morning from then out. Lots of adrenaline with body rushes and loose stools. A lot of salt, sugar, and water calmed that down. But soon after the subject started to notice incredible energy. There was a very strong desire to work out, like never before. There was some manual labor at work, and his endurance was way up, though he did get out of breath.

Still an early report, but the subject is going to do a much lower dose next time (maybe 1 drop) and work on bag breathing and increased salt consumption before getting back up to a dose that might replace Cyproheptadine or some of the other supplements he's taking.

Thanks for the report. I personally do not use more than 10mg at once and repeat if needed a few times daily. I really like the sleep effects from 10mg before bed as at the lower dose it should be primarily anti-excitotoxic and anti-cortisol and so much dopaminergic and and simulating enough to disrupt sleep.
 
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Does anyone think this would pair with cypro well for reducing stress as well as pushing up dopamine? Been having great success with cypro but it leaves me feeling a little flat at times which I attribute to dopamine levels being low.

It may be too much of an anti-cholinergic effect when taken together. I think adamantane is best used on its own, at least until the proper dose is gauged. It should be anti-serotonin by itself so maybe not much need to add another serotonin blocker like cypro.
 

DKayJoe

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It may be too much of an anti-cholinergic effect when taken together. I think adamantane is best used on its own, at least until the proper dose is gauged. It should be anti-serotonin by itself so maybe not much need to add another serotonin blocker like cypro.

Ok, thanks for the prompt response! My current regimen seems to be stable at the moment so I will probably give this a miss for now and tweak lifestyle/other supplements. Super props as usual for sticking such an interesting product out there!
 

Pointless

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Thanks for the report. I personally do not use more than 10mg at once and repeat if needed a few times daily. I really like the sleep effects from 10mg before bed as at the lower dose it should be primarily anti-excitotoxic and anti-cortisol and so much dopaminergic and and simulating enough to disrupt sleep.

Yes, the subject has had trouble sleeping the past two nights, and he even had restless legs which is rare for him, so the doses used were definitely too much. 2 drops of Lapodin and he nodded off but not a totally restorative sleep.

It may be too much of an anti-cholinergic effect when taken together. I think adamantane is best used on its own, at least until the proper dose is gauged. It should be anti-serotonin by itself so maybe not much need to add another serotonin blocker like cypro.

I can vouch that combining Cyproheptadine and Adamantane increases the dry mouth effect so that's a bit of a deterrent to combining these.
 

Name1

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Yes, here it is. Not only was adamantane extremely potent HDAC inhibitor by itself but messing with its structure reduced that activity and its anti-cancer effects.
"...Initially we started our SAR studies with unsubstituted adamantane, (compound 5) which shows the HDAC inhibitory activity about 70 nM with 0.5-2.8 µM range of anti-cancer activity. Replacing hydrogen in 3rd position of 5 with ethoxy, methoxy, hydroxyl, phenyl and hydroxymethyl (compounds 6, 7, 8, 9 & 10), decreased the potency against HDAC as compared to 5 by 3 fold and the anti-cancer activity also reduced."

If you look at Table 1, compound 5 is the following:

upload_2017-3-20_17-9-9.png


Clearly not an unsubstituted adamantane (C10H16). 'Unsubstituted' in the context of the paper means only mono-substituted (The N-hydroxy 4-aminomethylcinamide (or similar) replacing a hydrogen). 'Substituted' (in the context of the paper) means di-substituted on the adamantane moiety.

Where in the paper is the HDAC inhibition activity of unsubstituted adamantane (C10H16) measured?
 
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If you look at Table 1, compound 5 is the following:

View attachment 4878

Clearly not an unsubstituted adamantane (C10H16). 'Unsubstituted' in the context of the paper means only mono-substituted (The N-hydroxy 4-aminomethylcinamide (or similar) replacing a hydrogen). 'Substituted' (in the context of the paper) means di-substituted on the adamantane moiety.

Where in the paper is the HDAC inhibition activity of unsubstituted adamantane (C10H16) measured?

Let me search through my notes. It's been a while since I looked at that link. I am pretty sure I emailed the authors about unsubstituted adamantane and they said it was also inhibitory. As far as I remember, this is one of the studies they sent me. I know it's still not pure adamantane, so I will find their email and post it here.
Neuropsychopharmacology - Novel Neuroprotective Mechanisms of Memantine: Increase in Neurotrophic Factor Release from Astroglia and Anti-Inflammation by Preventing Microglial Activation
"...Thus, we determined whether the HDAC activity is affected in the cellular levels of astroglia treated with memantine (10 μM). ANOVA analysis showed a significant main effect among these groups (F(5, 12)=28.95, p<0.001) (Figure 4b). The cellular HDAC activity in memantine-treated astroglia was significantly suppressed at 2 h (t=5.73, p<0.01), maximally at 4 h (t=10.77, p<0.001), and at 12 h (t=5.37, p<0.01), compared with the controls with post hoc analysis (Figure 4b). We also compared the effects of VAP (1 mM), a widely used HDAC inhibitor, and memantine (10 μM) on the HDAC activity of astroglia at 4 h after administration. The activity was almost equipotently inhibited about 30% by either memantine or VPA (t=0.43, p>0.5, Student's t-test). These results indicate that memantine and VPA inhibited HDAC activity in different mechanisms. Therefore, we examined whether changes of histone acetylation levels occur at the GDNF promoter region by ChIP study. The result showed that markedly enhanced association of acetylated H4 for one (Pc) (F(2, 6)=66.33, p<0.001, Figure 4c) out of these three primer set regions was observed in the memantine-treated astroglia. Post hoc analysis showed that the levels of acetylation of Pc region were significantly increased at 1 h (t=6.48, p<0.05), and 4 h (t=11.49, p<0.001) (Figure 4c), indicating that memantine triggered recruitment of acetylated histone, specifically to the proximally close to the initiator site of GDNF gene."

Also, a lot of the rationale for using unsubsituted adamantane as the actual supplement comes from this extensive review below, which I posted in the original thread. That review focuses on the parent compound - the unsubstituted adamantane, and it various properties and benefits. It concludes that it is the adamantane itself, and not its various modifications, that is responsible for the plethora of benefits observed with all of those chemical derivatives.
The Lipophilic Bullet Hits the Targets: Medicinal Chemistry of Adamantane Derivatives
"...We will not elaborate on the development of pharmaceuticals from oxaadamantanes, azaadamantanes, or any other heteroadamantanes, that could be viewed as inspired by natural products. There are, however, also natural products that incorporate the adamantane skeleton,1921 some of which also display interesting biological properties. This review focuses on the medicinal chemistry of the parent hydrocarbon, adamantane, and its derivatives. "
 
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