PSSD Forum

What are other people noticing? Ordered reboxetine from a place in Spain...hoping it doesnt take forever to get here.

Atomoxetine also antagonizes GIRK in the heart and brain (reboxetine also):

Kobayashi T, Washiyama K, Ikeda K (June 2010). "Inhibition of G-protein-activated inwardly rectifying K+ channels by the selective norepinephrine reuptake inhibitors atomoxetine and reboxetine". Neuropsychopharmacology. 35 (7): 1560–9. doi:10.1038/npp.2010.27. PMC 3055469. PMID 20393461.
https://en.wikipedia.org/wiki/Atomoxetine#Pharmacology

I cant tell if it would be a better trial rather than reboxetine. Anyone?

Atomoxetine is less selective is also NMDA antagonist.

https://www.bionity.com/en/encyclopedia ... de_effects

side effect of reboxetine: "increased orgasm intensity"

ive been doing sjw (500mg, couple days 1000mg), with lecithin. currently i have a short break like beetlebum did after 10 days, but i will get back on it tomorrow.
i had clear benefits on libido and emotions, with some side effects like numbness, very similar to what beetlebum reported.

will be interesting to see what happens in the coming weeks. i dont see any benefits from lecithin specifically, but in the past the effects of sjw always decreased after a while, perhaps it helps on this aspect.

tbc

Jaxx wrote: ↑Tue Dec 14, 2021 5:15 pm ive been doing sjw (500mg, couple days 1000mg), with lecithin. currently i have a short break like beetlebum did after 10 days, but i will get back on it tomorrow.
i had clear benefits on libido and emotions, with some side effects like numbness, very similar to what beetlebum reported.

will be interesting to see what happens in the coming weeks. i dont see any benefits from lecithin specifically, but in the past the effects of sjw always decreased after a while, perhaps it helps on this aspect.

tbc

Hope u don't get crash man. Very different opinions of using sjw.

Took my first dose of reboxetine today, 2mg. Feel high and a bit tired. How long should it take to upregulate GIRK and will it be permanent upregulation (in theory)?

guacamo wrote: ↑Mon Dec 06, 2021 7:18 am Take note

Hows your research going?

My experience last night with 2mg reboxetine was somewhat confusing. 2 mg reboxetine produced almost everything I would expect from a dose of ecstasy. Pleasant tingling all over, very relaxed, very sexual, feeling amazing. Contrary to ecstasy , 1 hr into it, it was impossible to get it up and I had two ejaculations while completely soft, the first one, i felt no orgasm, the second one, I did. Felt very cold, very sleepy, but I got brain zaps when I tried to go to sleep soon afterward that kept me up. About 2 to 2.5 hrs in, I felt anxious and some tighness in the chest. Got another brain zap while trying to fall asleep so I kept myself up for another 4 or 5 hrs doing chores around my apartment. Noticed some penis numbness, and strong brain activation.

Would suggest starting at 1mg for other people trying reboxetine.

Expected sexual dysfunction from GIRK antagonism and the reputation of the drug but I am hoping that GIRK receptor antagonism leads to upregulation over time. What would be an example of a GIRK receptor agonist?

Saw this on the GIRK wiki page: "A wide variety of G protein-coupled receptors activate GIRKs, including the M2-muscarinic, A1-adenosine, α2-adrenergic, D2-dopamine,
μ- δ-, and κ-opioid, 5-HT1A serotonin, somatostatin, galanin, m-Glu, GABAB, TAAR1, CB1 and CB2, and sphingosine-1-phosphate receptors"

I do not think that taking reboxetine is the way to go. There are two ways of how desensitization works. There is heterologous desensitization where ligand no longer exert cellular response in the receptor. After this happens receptor becomes internalized. This is what i think is happening in PSSD. The other desesensitization is homologous desensitization where signal transduction exerted by the receptor is broken, like serotonin no longer activates G proteins. They both happen in PSSD, but homologous desensitization in this case is a result of heterologous desensitization caused by extreme serotonin levels in the raphe nuclei. So i think logic would tell us that you cannot make 5-HT1A receptor activate g protein no matter how sensitive g proteins are, because it is simply what internalized receptors do. So to make it work right one should work towards making 5-HT1A receptors not be internalized anymore, that would cause the whole cascade to work again. I think no matter how much GIRK antagonist one will take, it wont overcome the fact that 5-HT1A receptor is internalized and will not activate them no matter what. Anyone more interested in the topic i advice to look on this robust paper on GIRK channel
https://scholarscompass.vcu.edu/cgi/vie ... ontext=etd.
The thing is excess PIP2 levels can instead of activating GIRK2 or GIRK3 in 5-HT1A mediated transduction, go and activate Gqs proteins that go on and activate Protein Kinase C that is a direct inhibitor of GIRK channels by inhibiting their affinity for PIP2 , so one can actually inhibit GIRKs by taking inositol instead of activating it. That is something thats need to be overcomed, and in cases where taking inositol helped there could be that in the brains of these people PIP2 went directly to GIRKs instead of activating PKC. I also found a paper which stated that hypericin from st john wort is Protein Kinase C inhibitor, which can contribute to it's anti-anhedonic effect on PSSD. But surely there is something missing, something that needs to be overcomed in order to change the whole chain of cellular effects. But st john wort is not potent enough inhibitor to overcome the inositol mediated PKC activation if that is the case. I did read on the forum that one person stated that drinking wine provides relief of the symptoms, grape contain miyabenol C that inhibits PKC.

https://journals.plos.org/plosone/artic ... ne.0204447

Gi/o-coupled muscarinic receptors co-localize with GIRK channel for efficient channel activation