Opiesdad improves on:
Bupropion and propranolol. Feels worse on SSRI's and LDN.
Hurray improves on Milnacipran while various SNRI's did not do anything for him, feels worse on some (serotonin?):
"There are several drugs which boost norepinephrine, so why is milnacipran any different?"
Well, I have already tried several NRIs:
atomoxetine (Strattera) - uncomfortable feeling during O, brain fog remained
buproprion - made me feel jittery, brain fog remained
ritalin - gave me energy and focus before quickly building up tolerance, did not stop the brain fog
duloxetine - felt like bad flu, could not drive or work, withdrawal symptoms, too sick to accurately gauge brain fog
venlafaxine - felt like bad flu, could not drive or work, bad withdrawal symptoms, too sick to accurately gauge brain fog
The effects of duloxetine and venlafaxine (both SNRIs) were interesting. They made me feel terrible - there was no way that I could take them every day. But my POIS felt a bit different while I was on both drugs.
I read that duloxetine and venlafaxine don't have a powerful effect on norepinephrine at low doses. There was only a substantial norepinephrine reuptake inhibition effect at high doses.
Venlafaxine has potency at serotonin transporters which is about 30-fold greater than that at norepinephrine transporters while milnacipran has a similar potency at each transporter. Thus, at low doses, venlafaxine acts essentially as a SSRI, with significant noradrenergic activity only occurring at higher doses.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819762/
Trying milnacipran, I was surprised to find that a low one-off dose was sufficient to completely stop the POIS brain fog that I have been accustomed to for so many years. I attributed this to the powerful effect that milnacipran has on norepinephrine reuptake inhibition.
Milnacipran also has multiple reports that it cured the brain fog of fibromyalgia sufferers.
They both feel improvements faster than what the meds are indicated for (usually take weeks for (full) effect).
Is the great common denominator in this story Norepinephrine? Both
Bupropion and
milnacipran are able to inhibit TNF-alpha as well.
Hurray's PE improved -->
Milnacipran for Postcoital Cephalgia and Premature Ejaculation (Article can be found under PE in POIS paper archive thread).
Since Bupropion is more effective for Opiesdad than propranolol, it could indicate that there is something going on with dopamine and thus could have consequences for norepi levels (or bupropion is more efficient in raising Norepi?). More about the neuroendocrine response to orgasm can be found
here.
(Nor)epinephrine is also a
mast cell stabilizer, SSRI's have a
high risk of mast cell activation (the reason he feels worse on SSRI's?). Epinephrine can inhibit TNF release from MCs and could explain anti-inflammatory effects of the above meds:
ritalin - gave me energy and focus before quickly building up tolerance, did not stop the brain fog
Ritalin can also raise DA and NE in brain if I'm not mistaken. Overlap with this?:
I first managed it with Dextroamphetamine which is used for ADHD but now not even that helps
From cocaine thread:
From tuning the brain:
"Androgens such as testosterone increase the secretion of dopamine, probably by decreasing the activity of the dopamine transporter. Ritalin and cocaine also have this action. Androgens also increase DA by interacting with NO"
"Adderall works both by inhibition of dopamine reuptake and by increasing secretion of norepinephrine and dopamine. Inhibition of dopamine reuptake by blocking the plasma membrane dopamine transporter is the primary mechanism of action of methylphenidate (MPH, Ritalin) and cocaine."
Nitroglycerin may work as well. I bet this is one of the possible pathophysiologies of POIS.
Should mention that in the 2020 case study reporting an effective treatment of a single patient using TRT, the report mentions in the history that the patient had not had good results with Wellbutrin among other therapies, so it won't work for everyone I guess.
He is talking about #29 (mind you numbers may change):
https://poiscenter.com/forums/index.php?topic=3551.0If hCG works for patient from article #29 then why isn't Bupropion when considering DA?:
https://poiscenter.com/forums/index.php?topic=3551.msg38085#msg38085IDK 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 beta-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.
Relationship Between Amyloid Precursor Protein in Seminal Plasma and Abnormal Penile Sympathetic Skin Response in Lifelong Premature EjaculationCompare with
Milnacipran for Postcoital Cephalgia and Premature Ejaculation.
Edit:
Hi Muon,
Regarding your post on Bupropion :
Opiesdad improves on: Bupropion and propranolol. Feels worse on SSRI's and LDN.
(...)
You may want to read this exchange on reddit (user TheLooza is Opiesdad), for other hypotheses :
https://www.reddit.com/r/POIS/comments/mkeh4n/wellbutrin_appears_to_have_cured_my_worst_symptoms/gtjjz8z/?context=3
and https://www.reddit.com/r/POIS/comments/mrp51k/noepiephrine_deficiency_and_noepiephrine_reuptake/guwbi6p/?context=3