I am taking NSI-189 as a trial to try and fix my ongoing severe memory loss associated with Idiopathic Hypersomnia (See previous threads)
I have been on a number of SSRIs and SNRIs over the years and have been on NSI-189 on and off for about two weeks now, the best way I would describe NSI-189 is that it feels like an SSRI but its side effects are less intense and it offers a faster mechanism of action.
I got many of the symptoms of an SSRI, emotional flattening, sometimes emotional intensity which caused rage on one occasion and caused me to cry to music a few times, mydriasis, nausea, vascular effects, daytime sleepiness increased greatly and nighttime insomnia, so at first I didn't believe the narrative that they could not find any receptor bindings to Serotonin however I can mix 60mg of it with Sertraline, normally that jump in a single day would give me Serotonin syndrome.
When I take NSI-189 with Sertraline it removes Sertralines vasodilation effects, I also feel happier and less angry but I saw no real benefit with combining the two, I find when mixing anti-depressants one tends to just override the other and I am guessing that is what it did.
If I were to guess I would say NSI-189 is releasing Serotonin but doing it in some unknown and a more controlled way because I cannot explain how its side effects so closely match an SSRI without it working on Serotonin, I maybe wrong but what else could cause emotional flattening, anger, mydriasis and nausea?
The big difference for me compared to an anti-depressant was how fast it works, within a day I get memory improvement, even at 10mg I feel it slightly, normally it takes about 2 weeks with Sertraline to give any memory benefit for me and I have to build it up to 100mg, which is when Sertraline becomes a potent SDRI, we know from studies of SSRIs that they begin working at 2 weeks of reputake and start releasing dopamine (Sertraline does this strongly at 100mg) we also see neurogenesis with continued use.
So from my anecdotal experience, NSI-189 appears to be a rapidly acting anti-depressant, it has more tolerable side effects than most SSRIs/SNRIs, I would recommend it for those who want an anti-depressant but do not want to wait months for an SSRI/SNRI to kick in or are having a lot of trouble managing their side effects.