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Re: An Excellent Explaination of How SSRI's Inhibit Sert
Posted: Wed Dec 28, 2022 12:36 am
by Tree
wardeath wrote: ↑Mon Dec 26, 2022 11:57 am
How can we get this medication?
No idea but I'll try it as soon as I can
Re: An Excellent Explaination of How SSRI's Inhibit Sert
Posted: Wed Dec 28, 2022 12:50 pm
by wardeath
Tree wrote: ↑Wed Dec 28, 2022 12:36 am
wardeath wrote: ↑Mon Dec 26, 2022 11:57 am
How can we get this medication?
No idea but I'll try it as soon as I can
Are their any other ways to upregulate sert?
Re: An Excellent Explaination of How SSRI's Inhibit Sert
Posted: Sat Dec 31, 2022 12:48 am
by Tree
wardeath wrote: ↑Wed Dec 28, 2022 12:50 pm
Tree wrote: ↑Wed Dec 28, 2022 12:36 am
wardeath wrote: ↑Mon Dec 26, 2022 11:57 am
How can we get this medication?
No idea but I'll try it as soon as I can
Are their any other ways to upregulate sert?
I haven't been able to find any other drug or supplement able to raise sert in the dorsal raphe, which this drug is reported to do. It seems to work in complete opposite of ssris. This is exciting.
Re: An Excellent Explaination of How SSRI's Inhibit Sert
Posted: Sat Dec 31, 2022 6:12 pm
by fellow1
Tree wrote: ↑Sat Dec 31, 2022 12:48 am
wardeath wrote: ↑Wed Dec 28, 2022 12:50 pm
Tree wrote: ↑Wed Dec 28, 2022 12:36 am
No idea but I'll try it as soon as I can
Are their any other ways to upregulate sert?
I haven't been able to find any other drug or supplement able to raise sert in the dorsal raphe, which this drug is reported to do. It seems to work in complete opposite of ssris. This is exciting.
Wtf, can you guys read ? It's does the same thing as SSRI, DISRUPTING SERT- NNOS. Disrupting= downregulating.
Disrupting the SERT-nNOS interaction produced a fast-onset antidepressant effect by enhancing serotonin signaling in forebrain circuits. We discovered a small-molecule compound, ZZL-7, that elicited an antidepressant effect 2 hours after treatment without undesirable side effects.
Re: An Excellent Explaination of How SSRI's Inhibit Sert
Posted: Sat Dec 31, 2022 8:13 pm
by Tree
fellow1 wrote: ↑Sat Dec 31, 2022 6:12 pm
Tree wrote: ↑Sat Dec 31, 2022 12:48 am
wardeath wrote: ↑Wed Dec 28, 2022 12:50 pm
Are their any other ways to upregulate sert?
I haven't been able to find any other drug or supplement able to raise sert in the dorsal raphe, which this drug is reported to do. It seems to work in complete opposite of ssris. This is exciting.
Wtf, can you guys read ? It's does the same thing as SSRI, DISRUPTING SERT- NNOS. Disrupting= downregulating.
Disrupting the SERT-nNOS interaction produced a fast-onset antidepressant effect by enhancing serotonin signaling in forebrain circuits. We discovered a small-molecule compound, ZZL-7, that elicited an antidepressant effect 2 hours after treatment without undesirable side effects.
It decreases serotonin by increasing sert in the Raphe I've found no other drug capable of doing that
Re: An Excellent Explaination of How SSRI's Inhibit Sert
Posted: Sat Dec 31, 2022 8:20 pm
by Tree
Tree wrote: ↑Sat Dec 31, 2022 8:13 pm
fellow1 wrote: ↑Sat Dec 31, 2022 6:12 pm
Tree wrote: ↑Sat Dec 31, 2022 12:48 am
I haven't been able to find any other drug or supplement able to raise sert in the dorsal raphe, which this drug is reported to do. It seems to work in complete opposite of ssris. This is exciting.
Wtf, can you guys read ? It's does the same thing as SSRI, DISRUPTING SERT- NNOS. Disrupting= downregulating.
Disrupting the SERT-nNOS interaction produced a fast-onset antidepressant effect by enhancing serotonin signaling in forebrain circuits. We discovered a small-molecule compound, ZZL-7, that elicited an antidepressant effect 2 hours after treatment without undesirable side effects.
By dissociating nNOS it decreases serotonin by increasing sert in the Raphe. I've found no other drug capable of doing that.
Re: An Excellent Explaination of How SSRI's Inhibit Sert
Posted: Thu Jan 12, 2023 5:38 am
by Answers
This is really confusing to because I thought we had to raise nitric oxide and that it was beneficial to do so. But if doing that decreases SERT then this sucks.
All this seems to be is one contradiction after another
Re: An Excellent Explaination of How SSRI's Inhibit Sert
Posted: Fri Jan 13, 2023 3:15 am
by Tree
There are several different nitric oxide isoforms but not all of these isoforms might be bad for pssd. It appears though that too much neuronal nitric oxide or nNOS inhibits sert in the Dorsal Raphe. Increased nNOS may not be the cause of pssd, but we might get symptom relief at least, if nnos inhibits sert less effectively from ZZL-7.
Re: An Excellent Explaination of How SSRI's Inhibit Sert
Posted: Fri Jun 30, 2023 3:33 am
by Tree
Here we see the chronic effects on the brain's serotonin system where the feedback 5-HT1A is internalized/desensitized and damaged by uncoupling from it's g-protein and losing part of it's function. But these recover after discontinuation, only the transporter SERT is actually degraded over time and does not restore. The situation that is somewhat similar as having a genetic short allele and low expression of SERT.
Effects of the antidepressant fluoxetine on the subcellular localization of 5-HT1A receptors and SERT
ABSTRACT
Serotonin (5-HT) 5-HT1A autoreceptors (5-HT1AautoR) and the plasmalemmal 5-HT transporter (SERT) are key elements in the regulation of central 5-HT function and its responsiveness to antidepressant drugs. Previous immuno-electron microscopic studies in rats have demonstrated an internalization of 5-HT1AautoR upon acute administration of the selective agonist 8-OH-DPAT or the selective serotonin reuptake inhibitor antidepressant fluoxetine. Interestingly, it was subsequently shown in cats as well as in humans that this internalization is detectable by positron emission tomography (PET) imaging with the 5-HT1A radioligand [18F]MPPF. Further immunocytochemical studies also revealed that, after chronic fluoxetine treatment, the 5-HT1AautoR, although present in normal density on the plasma membrane of 5-HT cell bodies and dendrites, do not internalize when challenged with 8-OH-DPAT. Resensitization requires several weeks after discontinuation of the chronic fluoxetine treatment. In contrast, the SERT internalizes in both the cell bodies and axon terminals of 5-HT neurons after chronic but not acute fluoxetine treatment. Moreover, the total amount of SERT immunoreactivity is then reduced, suggesting that SERT is not only internalized, but also degraded in the course of the treatment. Ongoing and future investigations prompted by these finding are briefly outlined by way of conclusion.
Re: An Excellent Explaination of How SSRI's Inhibit Sert
Posted: Mon Jul 03, 2023 4:17 am
by heymartinn
I wonder what abnormalities would SERT imaging show in a group of PSSD sufferers. Evidence of persistently lowered sert activity would not only be a great biomarker but also be a great aid in a class action lawsuit I suppose.
Those who are more educated on the technical stuff, let us know if it's even viable option:
https://www.frontiersin.org/articles/10 ... 00172/full