Author Topic: Milnacipran - completely stopping my brain fog  (Read 48624 times)

hurray

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Re: Milnacipran - completely stopping my brain fog
« Reply #100 on: August 08, 2020, 05:04:29 PM »
Have you tried NSAIDs hurray?

Yes, I sometimes take ibuprofen, but it doesn't seem to have any effect on my POIS symptoms.

Nas

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Re: Milnacipran - completely stopping my brain fog
« Reply #101 on: August 19, 2020, 11:37:18 AM »
IDK how significant is this but according to wikipedia: "Recently, levomilnacipran, the levorotatory enantiomer of milnacipran, has been found to act as an inhibitor of beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1), which is responsible for β-amyloid plaque formation, and hence may be a potentially useful drug in the treatment of Alzheimer's disease."

β-amyloid plaque formation causes irregular ion channel activity and BACE-1 is triggered by cytokine release.


hurray

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Re: Milnacipran - completely stopping my brain fog
« Reply #103 on: August 19, 2020, 03:48:31 PM »
IDK how significant is this but according to wikipedia: "Recently, levomilnacipran, the levorotatory enantiomer of milnacipran, has been found to act as an inhibitor of beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1), which is responsible for ?-amyloid plaque formation, and hence may be a potentially useful drug in the treatment of Alzheimer's disease."

?-amyloid plaque formation causes irregular ion channel activity and BACE-1 is triggered by cytokine release.

Interesting. Milnacipran's action of BACE-1 inhibition could be one of the reasons why milnacipran stops my brain fog.

hurray

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Re: Milnacipran - completely stopping my brain fog
« Reply #104 on: August 19, 2020, 04:11:31 PM »
Effects of paroxetine or milnacipran on serum brain-derived neurotrophic factor in depressed patients

Increasing BDNF levels could well be an important part of the puzzle regarding POIS. However, it appears that many different anti-depressants cause serum BDNF levels to increase. Also, in this case, an SSRI (paroxetine) was more effective than an SNRI (milnacipran). Another paper mentioned that fluoxetine (SSRI) was effective, whereas venlafaxine (SNRI) had little effect on BDNF levels.

Nas

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Re: Milnacipran - completely stopping my brain fog
« Reply #105 on: August 19, 2020, 08:42:07 PM »
Interesting. Milnacipran's action of BACE-1 inhibition could be one of the reasons why milnacipran stops my brain fog.

Note levomilnacipran and not milnacipran, however milnacipran might've still had the same effect. Unfortunately levomilnacipran is the only commercially available BACE-1 inhibitor.

hurray

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Re: Milnacipran - completely stopping my brain fog
« Reply #106 on: August 20, 2020, 04:25:32 AM »
Interesting. Milnacipran's action of BACE-1 inhibition could be one of the reasons why milnacipran stops my brain fog.

Note levomilnacipran and not milnacipran, however milnacipran might've still had the same effect. Unfortunately levomilnacipran is the only commercially available BACE-1 inhibitor.

That's a good point, Nas. It would be very interesting to know if levomilnacipran stopped my POIS brain fog in the same way as milnacipran.

Vandemolen

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Re: Milnacipran - completely stopping my brain fog
« Reply #107 on: August 22, 2020, 06:13:16 AM »
I have ordered Milnacipran too. Not available in The Netherlands, so I have to wait a while.
POIS since 2000. Very bad since 2008. I knew that I have POIS since June 2010. Desensitization since March 2011. I stopped with desens in July 2016. I have 50% less POIS. And only 1 day of POIS. Purified CBD works for me, but I am allergic for CBD.

hurray

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Re: Milnacipran - completely stopping my brain fog
« Reply #108 on: August 22, 2020, 08:35:46 AM »
I have ordered Milnacipran too. Not available in The Netherlands, so I have to wait a while.

Thank you for the update Vandemolen  :)

Vandemolen

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Re: Milnacipran - completely stopping my brain fog
« Reply #109 on: August 24, 2020, 08:59:06 AM »
Oh no, wrong topic. I ordered Pepto Bismal.
POIS since 2000. Very bad since 2008. I knew that I have POIS since June 2010. Desensitization since March 2011. I stopped with desens in July 2016. I have 50% less POIS. And only 1 day of POIS. Purified CBD works for me, but I am allergic for CBD.

hurray

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Re: Milnacipran - completely stopping my brain fog
« Reply #110 on: August 24, 2020, 10:20:26 AM »
Oh no, wrong topic. I ordered Pepto Bismal.

Easily done, Vandemolen  :)

Tijmen

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Re: Milnacipran - completely stopping my brain fog
« Reply #111 on: September 01, 2020, 05:59:00 AM »
Here's my theory on why milnacipran might work for pois:
When you O you get all kinds of hormones, bad ones and good ones. I think that our O's aren't intense enough to release enough good hormones. Milnacipran can increase internisity of O's. PE decreases intensity, this is also why I think we get stronger pois if we do it multiple times a day/ week. Because the O is less intense. I have had very few intense O's in my lifetime, but I remember with the ones I did have, I had no pois after. Hope this helps.  ;)

drop247

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Re: Milnacipran - completely stopping my brain fog
« Reply #112 on: September 01, 2020, 06:18:34 AM »
Interesting theory. Perhaps we are dealing with an infection of the prostate and an intense enough orgasm clears it out. Some people with prostatitis milk their prostate rectally to clear all areas of the gland of infection. This also produces an intense orgasm.

I've seen some people on reddit have success with lowering POIS by having multiple orgasms in a short period. Which perhaps accomplishes the same thing.

Muon

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Re: Milnacipran - completely stopping my brain fog
« Reply #113 on: September 01, 2020, 08:06:12 AM »
Perhaps we are dealing with an infection of the prostate...

Elevated IL-8 in seminal fluid might be a potential marker for that.

Muon

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Re: Milnacipran - completely stopping my brain fog
« Reply #114 on: September 01, 2020, 12:23:48 PM »
Is it possible it raises norepi in certain parts of the brain more than other parts compared to other SNRI's?

hurray

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Re: Milnacipran - completely stopping my brain fog
« Reply #115 on: September 01, 2020, 12:30:50 PM »
Here's my theory on why milnacipran might work for pois:
When you O you get all kinds of hormones, bad ones and good ones. I think that our O's aren't intense enough to release enough good hormones. Milnacipran can increase internisity of O's. PE decreases intensity, this is also why I think we get stronger pois if we do it multiple times a day/ week. Because the O is less intense. I have had very few intense O's in my lifetime, but I remember with the ones I did have, I had no pois after. Hope this helps.  ;)

That's an interesting theory. I have always experienced fewer POIS symptoms after a strong O, and having Os less often gives me less POIS.

Strength of O affecting POIS has been discussed on here many times - some people say strong is better, others say weak  :) But strong is certainly best for me.

berlin1984

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Re: Milnacipran - completely stopping my brain fog
« Reply #116 on: September 01, 2020, 12:44:03 PM »
Milnacipran was developed as a cure for fibromyalgia, but it has a secondary use as an antidepressant.

Fibromyalgia ? Neuroinflammatory Disease? Savella ? Anti- Inflammatory Drug?
https://www.healthrising.org/blog/2015/10/14/fibromyalgia-neuroinflammatory-disease-savella-anti-inflammatory-drug/
"This oxidative stress could result from glial cell activation, low antioxidant levels, or perhaps most likely ? both. Those isoprostanes then reduce blood flows and oxygen delivery to the brain by constricting the blood vessels in the brain. The low oxygen levels then reduce aerobic energy production and increase anaerobic energy production leading to high lactate levels.
Another hypothesis by Newton suggests that pH handling problems in the muscles could prompt  blood vessel constriction and the restriction of blood flows in the brain.
(Low blood flows (ischemia) can also set up the blood vessels for a free radical explosion when more normal blood flows return. Could an ischemic environment contribute to the PEM that occurs when some people with ME/CFS try to concentrate ? and thus send more blood flows to their brain?)"

^ posting those quotes since we had blood flow discussions in the forum some weeks ago. Yes I know that this is about Fibromyalgia not about POIS.

There's some more blogposts here: https://www.healthrising.org/blog/category/treatment/drugs/savella/


hurray

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Re: Milnacipran - completely stopping my brain fog
« Reply #117 on: September 01, 2020, 12:54:56 PM »
Is it possible it raises norepi in certain parts of the brain more than other parts compared to other SNRI's?

That is certainly a possibility. I don't know if any research has been done with regards to SNRI effects on specific parts of the brain - that would be very interesting.

The most striking difference between the SNRIs seems to involve their potency ratios. The two most popular SNRIs (duloxetine and venlafaxine) have an imbalanced potency ratio which greatly favours serotonin over norepinephrine.

Quote
Milnacipran has the most balanced potency ratio for reuptake inhibition of the two neurotransmitters compared with other SNRIs (1:1.6 for milnacipran, 1:10 for duloxetine, and 1:30 for venlafaxine), and in some studies milnacipran has been shown to inhibit norepinephrine uptake with greater potency than serotonin (2.2:1).

This quote seems to imply that you would need to take large doses of venlafaxine in order for it to have a similar effect to low dose milnacipran:

Quote
Venlafaxine has a much greater affinity for the 5-HT transporter than for the NE transporter. At low doses, it probably inhibits almost exclusively the 5-HT transporter, acting like a SSRI, with significant NE reuptake inhibition only occurring at higher doses.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938282/

Milnacipran: a unique antidepressant?
Siegfried Kasper and Gerald Pail
« Last Edit: September 01, 2020, 02:33:57 PM by hurray »

hurray

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Re: Milnacipran - completely stopping my brain fog
« Reply #118 on: September 01, 2020, 02:29:58 PM »
Milnacipran was developed as a cure for fibromyalgia, but it has a secondary use as an antidepressant.

Fibromyalgia ? Neuroinflammatory Disease? Savella ? Anti- Inflammatory Drug?
https://www.healthrising.org/blog/2015/10/14/fibromyalgia-neuroinflammatory-disease-savella-anti-inflammatory-drug/
"This oxidative stress could result from glial cell activation, low antioxidant levels, or perhaps most likely ? both. Those isoprostanes then reduce blood flows and oxygen delivery to the brain by constricting the blood vessels in the brain. The low oxygen levels then reduce aerobic energy production and increase anaerobic energy production leading to high lactate levels.
Another hypothesis by Newton suggests that pH handling problems in the muscles could prompt  blood vessel constriction and the restriction of blood flows in the brain.
(Low blood flows (ischemia) can also set up the blood vessels for a free radical explosion when more normal blood flows return. Could an ischemic environment contribute to the PEM that occurs when some people with ME/CFS try to concentrate ? and thus send more blood flows to their brain?)"

^ posting those quotes since we had blood flow discussions in the forum some weeks ago. Yes I know that this is about Fibromyalgia not about POIS.

There's some more blogposts here: https://www.healthrising.org/blog/category/treatment/drugs/savella/

The concept of ventricular lactate being a potential biomarker for fibromyaglia is a good one - as you say, what applies to FM may apply to POIS. The scientific study which healthrising.org based its article on is worth reading:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630071/

An article in Science Daily speculates that lactate (lactic acid) causes the brain to release more norepinephrine:

https://www.sciencedaily.com/releases/2014/02/140211084053.htm
https://sci-hub.tw/10.1038/ncomms4284

Muon

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Re: Milnacipran - completely stopping my brain fog
« Reply #119 on: September 02, 2020, 10:06:13 AM »
IDK how significant is this but according to wikipedia: "Recently, levomilnacipran, the levorotatory enantiomer of milnacipran, has been found to act as an inhibitor of beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1), which is responsible for ?-amyloid plaque formation, and hence may be a potentially useful drug in the treatment of Alzheimer's disease."

Beta-amyloid plaque formation causes irregular ion channel activity and BACE-1 is triggered by cytokine release.

From an experimental point of view, I always found Clomid (testosterone booster) to be helpful with my POIS. In fact I am in the process of buying some more, as my supply has almost run out.

I also had some positive experiences with testosterone gel dating back almost 20 years - it was prohibitively expensive back then, but I am sure the costs will have come down since then  :)

Testosterone reduces neuronal secretion of Alzheimer's beta-amyloid peptides

Beta-amyloid plaque formation causes irregular ion channel activity and BACE-1 is triggered by cytokine release.

Irregular ion channel activity
« Last Edit: September 02, 2020, 11:32:01 AM by Muon »