Strong case for dopamine

This is for hypothesis and even educated speculation.
Ykatan
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Re: Strong case for dopamine

Unread post by Ykatan »

6-eggs, how did you cure pssd?
kaimbre
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Re: Strong case for dopamine

Unread post by kaimbre »

I don't think PSSD is caused by low dopamine. The central theory is either the damaged 5-HT1A receptor (most accepted theory in the PSSD community) or the body's inability to convert testosterone to DHT - which is why some people recover on steroids. If the second theory is correct, this makes PSSD and SFP practically the same disease.
PSSD by a combination of Risperidon and Fluoxetin

Tests: damiana, gingko biloba, cabergolin, pramipexol, buspiron, SJW
Significant improvement only with SJW
DrugsAreBad
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Re: Strong case for dopamine

Unread post by DrugsAreBad »

kaimbre wrote: Wed Apr 26, 2023 9:08 am I don't think PSSD is caused by low dopamine. The central theory is either the damaged 5-HT1A receptor (most accepted theory in the PSSD community) or the body's inability to convert testosterone to DHT - which is why some people recover on steroids. If the second theory is correct, this makes PSSD and SFP practically the same disease.
That central theory has been around since the early 90s and has gone nowhere. It's likely just eating up resources that would be better spent elsewhere.
bupropioninducedPSSD
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Re: Strong case for dopamine

Unread post by bupropioninducedPSSD »

lukejimmy wrote: Fri Nov 18, 2022 11:08 am
6-Eggs! wrote: Thu Nov 17, 2022 8:26 pm Although this is all speculation. My neurologist which is regarded as one of the top ones in the Asia Pacific area said serotonin systems do fully recover but take months to a few years. Dopamine neurons take significantly longer and in some rarer cases only partly recover or not at all.

It's very easy to mess them up when taking any dopamine targeting drugs so I wouldn't risk it. Most people suffer issues long term from post ssri and other drugs due to trying to fix it with other treatments when the CNS is already hyper-sensitized and just prolongs the recovery and the cycle continues.
I agree with you on avoiding taking more drugs, but if dopamine targeting drugs caused long-term damage years post-discontinuation, then wouldn't there be a Post-Amphetamine Syndrome with 100'000's of people complaining about Numbed Positive Emotions, Anhedonia and Pleasureless Orgasm's, considering it's by far the most widely abused Prescription Medicine? I suppose there is a higher percentage of the Population on SSRI's but why isn't there a forum for an Amphetamine Post-Drug condition?
I also don't think SSRI's affect Dopamine Neurons in the same context where your Neurologist claims takes years or doesn't even recover at all, I assume the Hypersexuality/Porn addiction prevalence in PSSD victims would have a higher potential to do that given that it would be a more potent and direct effect on dopamine neurons vs SSRI's.
Speaking as one of the non-SSRI/SNRI folks (got it from Wellbutrin)—I'm a strongly science-oriented, research-oriented individual who only identified my PSSD (even the name is a misnomer in my case) a year after stopping Wellbutrin and two years after first experiencing symptoms. It's HARD to find this information because everywhere you look, you see people parroting the same misinformation ("Wellbutrin doesn't cause sexual side effects" etc). You have to reach deep into the data with exactly the right keywords to ever find PSSD. I suggest we broaden the name to antidepressant-related sexual dysfunction or even PMSD (post-medication sexual dysfunction) to cast the widest net and finally allow others to know what it is that's ruining life for them. Because most doctors would hear these symptoms and just prescribe Wellbutrin (which, though it seems of often work while you're on it—wreaks havoc when you come off. Of course, most people don't come off...or go back on soon after quitting).
Extremaduro
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Re: Strong case for dopamine

Unread post by Extremaduro »

My pssd caused by welbutrin too plus akathisia
OCDemon
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Re: Strong case for dopamine

Unread post by OCDemon »

Rexulti gave me PSSD. It affects dopamine D2 and D3 as well as serotonin 5-HT1A, primarily. I'll link to the Wiki description after my anecdote. Antipsychotics may be of particular interest re: dopamine. We need to consider people like me who have permanent sexual dysfunction and other changes after atypical antipsychotics. I will mention that in the distant past I was on Lexapro as well as Zyprexa. I wonder if years of those drugs predisposed me to being damaged by Rexulti, but who knows.

My main symptoms are *severe* premature ejaculation, and immediate loss of erection upon ejaculation -- basically, as soon as I start ejaculating, I start losing my erection. By the time I'm on the last muscle pulsations of an orgasm, I'm completely flaccid. My prior function was no premature ejaculation, and I would always maintain an erection for at least a minute after ejaculating, and sometimes after ejaculating, I would not lose my erection at all, and would be able to go for a "round 2" with no issues and just as much pleasure as the first time.

I have other symptoms such as extremely long refractory period, including numb/pleasureless orgasm after initial orgasm. i.e., I used to go for a "round 2" during sex in the past. Now, if I try to do that, if I'm even able to get an erection -- which is unlikely -- it will be completely numb, and orgasm will be pleasureless.

I've also had a very marked decrease, to the point of apparent complete absence, of the ability to feel romantic feelings. Even jealousy feels foreign to me now. I used to be extremely jealous, and I also used to have outbursts of rage on a regular basis. Once in a while I still get angry, but the rest of the emotions seem to have vanished. I will concede that I haven't been in any situations that would trigger these emotions, so it's possible I'm still able to feel them, but there have certainly been pronounced personality changes (such as being calmer/less emotional) that most of my friends have noticed.

I stopped Rexulti in 2019 and had a 2 month period of severe withdrawal. Cold turkey. Can't remember if my symptoms worsened over time or have stayed the same. It's possible quitting cold turkey made things worse but as I remember, things were already horribly bad while on the drug, and it's the reason I started researching it and decided to quit.

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Rexulti (Brexpiprazole) Wiki:

"
Brexpiprazole[20][21][22]
Site Human Ki (nM) Action Ref
5-HT1A 0.12 Partial agonist [21]
5-HT1B 32 ND [21]
5-HT2A 0.47 Antagonist [21]
5-HT2B 1.9 Antagonist [21]
5-HT2C 12–34 Partial agonist [21]
5-HT5A 140 ND [21]
5-HT6 58 Antagonist [21]
5-HT7 3.7 Antagonist [21]
D1 160 ND [21]
D2L 0.30 Partial agonist [21]
D3 1.1 Partial agonist [21]
D4 6.3 ND [21]
D5 ND ND ND
α1A 3.8 Antagonist [21]
α1B 0.17 Antagonist [21]
α1D 2.6 Antagonist [21]
α2A 15 Antagonist [21]
α2B 17 Antagonist [21]
α2C 0.59 Antagonist [21]
β1 59 Antagonist [21]
β2 67 Antagonist [21]
β3 >10,000 ND [21]
H1 19 Antagonist [21]
H2 >10,000 ND [21]
H3 >10,000 ND [21]
mACh 52% at 10 μM ND [21]
M1 67% at 10 μM ND [21]
M2 >10,000 ND [21]
σ 96% at 10 μM ND [21]
SERT 65% at 10 μM Blocker [21]
NET 0% at 10 μM Blocker [21]
DAT 90% at 10 μM Blocker [21]
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site. Most or all data are for human cloned proteins.

Brexpiprazole acts as a partial agonist of the serotonin 5-HT1A receptor and the dopamine D2 and D3 receptors.[21] Partial agonists have both blocking properties and stimulating properties at the receptor they bind to. The ratio of blocking activity to stimulating activity determines a portion of its clinical effects. Brexpiprazole has more blocking and less stimulating activity at the dopamine receptors than its predecessor, aripiprazole, which may decrease its risk for agitation and restlessness.[21] Specifically, where aripiprazole has an intrinsic activity or agonist effect at the D2 receptor of 60%+, brexpiprazole has an intrinsic activity at the same receptor of about 45%. For aripiprazole, this means more dopamine receptor activation at lower doses, with blockade being reached at higher doses, while brexpiprazole has the inverse effect because a partial agonist competes with dopamine.[23][24][25][26] Brexpiprazole has a high affinity for the 5-HT1A receptor, acting as a potent antagonist at 5-HT2A receptors, and a potent partial agonist at dopamine D2 receptors with lower intrinsic activity compared to aripiprazole.[27] In vivo characterization of brexpiprazole shows that it may act as a near-full agonist of the 5-HT1A receptor. This may further underlie a lower potential than aripiprazole to cause treatment-emergent, movement-related disorders such as akathisia due to the downstream dopamine release that is triggered by 5-HT1A receptor agonism. It is also an antagonist of the serotonin 5-HT2A, 5-HT2B, and 5-HT7 receptors, which may contribute to antidepressant effect. It also binds to and blocks the α1A-, α1B-, α1D-, and α2C-adrenergic receptors.[21] The drug has negligible affinity for the muscarinic acetylcholine receptors, and hence has no anticholinergic effects.[21] Although brexpiprazole has less affinity for H1 compared to aripiprazole, weight gain can occur.[28]"
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