#1

This is an interesting article:

The Pineal gland produces melatonin. According to some papers I have part of the melatonin goes into the third ventricle of the CSF and part goes into blood serum. According to one paper about sheep all goes into the CSF. Research should really be done into whether actually all of the pineal melatonin goes into the CSF or at least to get some ideas on proportions as it makes a big difference metabolically.

Obviously what goes into the CSF is likely to come out as well.

The concentration of melatonin in the CSF is 5-20 times as high as blood serum.

Hence when your brain is washed at night the concentration of melatonin is 5-20 times as high as blood serum.

This is one of the reasons why I started on higher dosing of melatonin. If my brain wants to be washed in melatonin at night then I would like to make sure that happens.

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#2

Interesting, thank you. I’ve been taking melatonin at various doses for many years. May I ask what you consider a high dose?

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#3

An interesting question. I take a range of doses each night between 10mg and over 900mg. I would think over 100mg is high, however.

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#4

What are your take on Agomelatine?

#5

Thank you. I’ve currently settled on about 50mg with 40 from bulk powder and 10 from a time released tablet. I suspected when I went higher than that it was leading to excessive hair shedding but it could have been a coincidence.

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#6

I had no awareness and have just looked at the wikipedia entry. I have no real comment to make.

#7

I would think any hair shedding is a coincidence. I will upload my current comparison photos. I am currently gradually reversing hair loss, it is a really slow process, but some of the things I do to modiify my metabolism are things which I don’t want to go too far on which may be needed to speed things up.

I do think the photos demonstrate what I see at a microscopic level which is an increase in new functioning hair follicles.

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When I say 100mg is high that is not to say personally that it is high for me. Although sometimes I don’t have as much exogenous melatonin, most nights I take more than 100mg.

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#8

Agomelatine is a melatonin analog and has a longer half-life and more significant affinity for melatonin-1 (MT-1) and melatonin-2 (MT-2) receptors than melatonin itself. Agomelatine has been shown to have antioxidant effects. It has been shown to increase the activity of antioxidant enzymes and reduce oxidative stress in various animal and cell models. In addition, some clinical studies have suggested that agomelatine may have antioxidant effects in humans as well.

https://www.scielo.br/j/bjps/a/xZNmYz6nZJ7TrqtJF9qzcPt/?format=pdf&lang=en

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#9

Looks good! Thanks for letting me know that it’s probably a coincidence.

#10

Bezesk, Have you used Agomelatine? If so, what are your thoughts? As a possible sleep aid what I’ve read says it’s great, but the smallest pill size is 25 mg which is in the clinical range for use as an antidepressant. I wouldn’t want the antidepressant effect which could mean withdrawal symptoms if used on a regular basis. The other potential problem is liver damage which is the reason it is not approved for use in the USA. Thanks.

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#11

@Jay I have been using it for a few months. i have been looking at solutions for better sleep that wouldn’t affect sleep architecture or might even promote deep sleep. Tried pregablin and trazodone without success. A colleague at the clinic suggested I try agomelatine 25mg, it is supposed to have almost no antidepressant effect at this dose and just promotes better sleep. My Apple Watch agrees, my sleep architecture is better and I went from average 30 minutes of deep sleep to 60 minutes. No other issues with it. Effect on liver is supposed to be negligible after first couple of weeks.
I started it taking cause my husband works early shifts and wakes up really early and I am a really light sleeper. Valdoxan helps me sleep less light and I wake up for few second when he gets up and fall back to sleep. I now regularly sleep 7.30-8 hours. I was wondering on its effects on longevity and after quick research I find it probably neutral to positive. I just got another prescription filled for 6 more months.
Oh and about withdrawal, if I forget to take it, the only effect is that I feel less sleepy and tend to go to bed an hour later and my sleep is a bit lighter and have difficulty to get back to sleep after I wake up when my husband wakes up. Sleep architecture recorded by Apple Watch looks immediately like before. I wake up more tired as a result.

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Suplementos para dormir: o que Ă© mais eficaz, menos viciante e mais seguro?
#12

I have commented in other threads about the use of quetiapine for sleep
If you have no problem getting to sleep but have a problem staying asleep, you might want to give quetiapine (Seroquel) a try. Yes, it is used for mood disorders, but the amount required for sleep extension is small compared to the therapeutic doses commonly used for mood disorders.
25 - 50 mg is the amount for sleep extension. Because of its long half-life, you need to take it about two hours before bedtime. It is cheap and available from the usual suspects in India.
I can find no adverse effects for long-term use, especially at the low doses needed for sleep extension.

#13

I have commented in other threads about the use of quetiapine for sleep
If you have no problem getting to sleep but have a problem staying asleep, you might want to give quetiapine (Seroquel) a try. Yes, it is used for mood disorders, but the amount required for sleep extension is small compared to the therapeutic doses commonly used for mood disorders.
25 - 50 mg is the amount for sleep extension. Because of its long half-life, you need to take it about two hours before bedtime. It is cheap and available from the usual suspects in India.
I can find no adverse effects for long-term use, especially at the low doses needed for sleep extension.

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#14

How quickly did you notice a positive effect on sleep? Have you tested liver values (ALT/AST) multiple times, and what were they like?

#15
#16

Worked with the first dose. I don’t think it needs a “loading” period. It is melatonin agonist so it works similarly to melatonin just more effective.

Yes, I did measure ALT (baseline 28.7, two weeks 33.7, one month 29.1 U/L) and AST (baseline 25.3, two weeks 27.6, one month 25.9 U/L)

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#17

Well, melatonin doesn’t work for me at all, but maybe I should still consider this.

#18

Melatonin doesn’t work for me either.

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#19

The first night’s experience with Valdoxan was bad; I couldn’t sleep at all, and even Zopiclone didn’t work, even though it usually does (I take it very rarely). However, I will continue testing it for at least a few more days.

#20

I am sorry to hear. When I first tried it I took it at around 10.30 PM and I usually go to bed way past midnight and that first day I was sleeping like dead on the sofa some 45 minutes later, but not in a drowsy way I just naturally get sleepy about an hour later.

Hope it will work for you. As I said I tried many things and beside lorazepam (which is certainly not something you would take long term) I get a terrible “hangover” in the morning or I struggle with cognition next day or it does nothing for my sleep.