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Agomelatine (valdoxan)

agomelatin valdoxan anxiety depression.

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6 replies to this topic

#1 Aj28

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Posted 21 March 2021 - 05:24 AM


Hey guys can you help me understand why would agomelatine trigger my anxiety?
I have been doing well since started taking agomelatine for insomnia. Although it helps insomnia, it triggers my anxiety and fight and flight response.

Also what's the difference with melatonin agonist such as agomelatine vs straight melatonin?

#2 Justin BoBustinBananaFanaF

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Posted 21 March 2021 - 10:47 PM

From wikipedia

"Agomelatine is a melatonin receptor agonist (MT1 (Ki 0.1 nM) and MT2 (Ki = 0.12 nM)) and serotonin 5-HT2C (Ki = 631 nM) and 5-HT2B receptor (Ki = 660 nM) antagonist..

By antagonizing 5-HT2C, it disinhibits/increases noradrenaline and dopamine release specifically in the frontal cortex."

My guess is it's either related to serotonin receptors or noradrenaline

Edited by Justin BoBustinBananaFanaF, 21 March 2021 - 10:49 PM.


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#3 kurdishfella

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Posted 21 March 2021 - 11:32 PM

A melatonin agonist drug would probably be stronger and longer lasting than regular natural melatonin thats the same (or very similar) to that  in your body, even though both are synthetic.  thought im not sure agomelatine has high affinity on the melatonin receptor(s?), its more an anti depressive drug but just happens to have some effect on the melatonin receptors by accident perhaps.


Edited by kurdishfella, 21 March 2021 - 11:39 PM.

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#4 Aj28

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Posted 22 March 2021 - 02:47 AM

Mirtazipine a 5ht1a inverse agonist , 5ht2a and 5ht2c antagonist kills my anxiety,

Trazodone a 5ht2a antagonist and 5ht2c agonist also helps my anxiety

But both make me feel like a zombie and exacerbate anhedonia

Buspirone on the other hand a 5ht1a agonist also helps my anxiety and helps with anhedonia and mood.

My doctor thinks I also have ADD which I started medication recently and they don't make my anxiety my worse. Bupropion also doesn't make my anxiety worse


I was thinking its either through melatonin? Which i dont think so, I have to try melatonin alone and test it.
Or agomelatine is an 5ht2a inverse agonist which is causing all kind of problems? Also a few days later it cause ED too!

#5 ErgogenicHealth

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Posted 27 March 2021 - 03:48 AM

Mirtazipine a 5ht1a inverse agonist , 5ht2a and 5ht2c antagonist kills my anxiety,

Trazodone a 5ht2a antagonist and 5ht2c agonist also helps my anxiety

But both make me feel like a zombie and exacerbate anhedonia

Buspirone on the other hand a 5ht1a agonist also helps my anxiety and helps with anhedonia and mood.

My doctor thinks I also have ADD which I started medication recently and they don't make my anxiety my worse. Bupropion also doesn't make my anxiety worse


I was thinking its either through melatonin? Which i dont think so, I have to try melatonin alone and test it.
Or agomelatine is an 5ht2a inverse agonist which is causing all kind of problems? Also a few days later it cause ED too!


5-HT2C plays a critical role in cortisol release. Have you used Cyproheptadine? 



#6 Aj28

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Posted 27 March 2021 - 07:41 AM

Yes funny that you ask as i am currently using it. Both times yield different results.

I decided to give it a try after thinking that my 5ht1a can possibly be desensitised since the use of buspirone (5th1a agonist) and since valdoxan triggered my anxiety out of nowhere. I was depressed but I didn't have anxiety. Now I am far less depressed with less anhedonia but my anxiety levels have been peaking(before the use of cyproheptadine)

After reading that 5ht1a knock-out in mice exhibit anxiety behaviour and less depression.
I decided to try cyproheptadine again.
https://www.ncbi.nlm...icles/PMC24398/


1st time I used it for 3 days.

2mg
It had knocked me out. Next day I was extremely sedated,dull and cranky, bad mood, heavily depressed and lethargic, aggressive and literally no motivation and brain dead.My apetite was also increased.Similar to mirtazapine.

My state was already depressed at the time so it seemes that it just exacerbated the problem. Medication was still the same the only thing I haven't tried was valdoxan and Ritalin.

This time round I have have used it for the last 3 days to sleep which doesn't work to well.
2 mg or 4 mg at night 3 hours before bed along side my low dose prescription Ritalin in the morning.

It doesn't knock me out, it has reduced my anxiety and it doesn't increase my appetite. I feel good. I dont feel sedated at all.
I know that cyproheptadine can reverse depression post ssri treatment so I was actually expecting to be kinda depressed but No.

I will discontinue it in a few days once I feel I have antagonised enough my 5ht1a and see what happens.

I am also sure that I have downregulated my 5ht2c receptor as mirtazipine and cyproheptadine doesn't make me hungry anymore.


I am also starting to believe 5ht2a antagonist for me cause anhedonia and here is why in very simple words.

Ritalin is a 5ht1a agonist https://pubmed.ncbi....h.gov/19322953/

At my current state I have no symptoms of anhedonia or depression, just mild anxiety. My 5ht1a gets agonised by the ritalin. Ritalin is a stimulant which suppresses apetite which makes me theorise that it must have some sort of a 5th2c effect as an antagonist through other mechanisms.

My 5ht2c is downregulated as I am never hungry anymore. Blockade by cyproheptadine is causing further downregulation. Therefore there must be more serotonin hitting my 5ht2a receptor which decreased my anhedonia.

Or it could just be ritalin increases my dopamine, cyproheptetine lowers my seratonin, therefore the positive outcomes.


I will update once I discontinue cyproheptadine.

Edited by Aj28, 27 March 2021 - 07:44 AM.


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#7 ErgogenicHealth

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Posted 25 May 2021 - 08:46 AM

Any updates man?







Also tagged with one or more of these keywords: agomelatin, valdoxan, anxiety, depression.

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