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notloki

The neurobiology of acetyl-L-carnitine

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2 hours ago, notloki said:

Like Keppra and Lethicin ?

Soy lecithin is more peripherally cholinergic, kinda like choline bitartrate. I was thinking more along the lines of alpha-GPC or CDP-choline, something like that. Possibly even centrophenoxine or DMAE, but between these two, centrophenoxine has greater blood-brain barrier permeability.

Well, levetiracetam is technically a racetam, so yes, but I was actually thinking more the prototypical piracetam and its other derivatives. Don't get me wrong, levetiracetam does appear to have antiamnesic and pro-cognitive effects that most of the other racetams do. They have recently started showing in studies for Alzheimer's disease that levetiracetam reduces hyperexcitability in the hippocampus (which I believe said helps with memory loss), reduces epileptiform activity that is typical in Alzheimer's disease (which helps with cognition), and, in short, can reverse cognitive decline and memory loss to some degree. Its little sibling, brivaracetam, has shown these capabilities too but to a greater extent, being that it is about 10x more potent than levetiracetam. So these two racetams could potentially have more pro-cognitive effects than we give them credit for.

Here's a bunch of links I've collected about this subject matter over time:

https://www.psypost.org/2015/05/epilepsy-drug-levetiracetam-could-help-treat-alzheimers-disease-34136

https://www.medicalnewstoday.com/articles/318113.php

https://www.medscape.com/viewarticle/747019

https://www.ncbi.nlm.nih.gov/pubmed/28527204

https://www.ncbi.nlm.nih.gov/pubmed/26268327

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3479491/

Seems like I had more, but I can't find them...

Anyway, like I said, I was thinking more piracetam, oxiracetam, aniracetam, pramiracetam, phenylpiracetam, nefiracetam, coluracetam, fasoracetam, Noopept (technically not a racetam but an AMPAkine), etc. They each have their own unique pharmacological profile, and depending on what you want out of it can dictate which one(s) you take; e.g,. if you want something calming, you would probably go more for aniracetam, or less commonly, nefiracetam, whereas if you want more stimulating ones, you could go for oxiracetam, pramiracetam, phenylpiracetam, and/or Noopept (Noopept is kind of in the middle, both calming and stimulating).

Fasoracetam is supposed to be good for ADHD, especially if you have mGluR mutations (it agonizes all three metabotropic glutamate receptors (mGluR). Aniracetam, coluracetam, and phenylpiracetam are supposed to be good for depression, so I've read. 

Aniracetam is a fat soluble racetam that is believed to reduce depression and anxiety (possibly a result of its effects on D2 and 5-HT2A receptors and probably others...) and increases memory/learning. It desensitizes AMPA glutamatergic receptors in your brain which increases the effectiveness of glutamatergic signaling resulting in better focus and concentration, and causes up to 200%-300% more acetylcholine release in your brain, leading to improved memory and recall. As an AMPAkine, it tends to be stimulating, but not amphetamine/methylphenidate-kind of stimulating. (Personally, aniracetam is sedating, and it is like that for some minority of people.) Anecdotally, it causes increased auditory perception and visual acuity, as well as sociability.

Nefiracetam, a fat soluble racetam, in addition to controlling NMDA receptor signalling, protecting against neuroexcitotoxicity from too much glutamatergic neurotransmission, as well as potentiating nicotinic acetylcholinergic receptors, boosting the release of both glutamate and GABA, it modulates GABA levels in the brain, reducing GABA levels when it's too high and increasing GABA levels when it's too low, enhancing GABAergic neurotransmission on GABAA receptors. That's just a few of its mechanisms of action. 

All of the racetams have some degree of anticonvulsant activity, but levetiracetam and brivaracetam are the two that are considered actual anticonvulsants. Piracetam has been noted to enhance the anticonvulsant activity of conventional anticonvulsants like carbamazepine.

If anyone wants me to go into more detail about the mechanisms of action into these, I'd be happy to. They're really fascinating to me. :)

There are other things you can combine with these to potentiate the above supplements, like acetyl-L-carinitine (ALCAR), which can help with cholinergic neurotransmission as well as help give a bit of an energy boost if needed, and, supposedly, sulbutiamine is a good one for energy (I don't feel anything from it personally... It's supposed to help with acetylcholine, dopamine, and GABA production, as well as upregulating D1 receptors receptors, and I think it does so via antagonism of these receptors, but I'm not certain about that...). 

Completed with a cholinergic supplement as aforementioned, you have a basic nootropic stack!

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I didn’t feel anything with the carnitine today. I think I’ll try 1k tomorrow. Is there a cut off time for taking it so it doesn’t interfere with sleep?

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1 hour ago, DammitJanet said:

I didn’t feel anything with the carnitine today.

Keep in mind that supplements are more like vitamins than meds. That means, they take time to work.

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3 hours ago, DammitJanet said:

I didn’t feel anything with the carnitine today. I think I’ll try 1k tomorrow. Is there a cut off time for taking it so it doesn’t interfere with sleep?

You need to give it a little time for it to work. You should probably not take the last dose any later than 1 PM I would say... That's how I do it anyway...

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On 1/27/2019 at 2:01 AM, notloki said:

Like Keppra and Lethicin ?

The PI (Prescribing Information) says Keppra can increase cognition, even my conservative neurologist said it could improve cognition. It is totally without side effects.  It is excreted mostly unchanged by the kidneys so it does not require the liver and will not react my other meds.

 

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