Ritanserin - Serotonin Antagonist For R&D Use Only

[haidut]

Any issues with taking this AND Bromocriptine???

Actually, the two could potentially make a killer combo. Hence why I am trying to get my hands on lisuride as well. See below.
The influence of antiserotonergic agents on the action of dopaminergic drugs. - PubMed - NCBI

"...The effect of drugs blocking serotonin receptors: cyproheptadine, methysergide, and methergoline, and of serotonin synthesis inhibitor, p-chlorophenylalanine on the stereotyped behavior and number of rearings of the rats receiving apomorphine, amphetamine, nomifensine and 1,3-dimethyl-5-aminoadamantane was investigated. The blockade of serotonin receptors potentiates behavioral effects of dopamine agonists. It is concluded that central serotonin may play an inhibitory role, antagonistic to that of catecholamines."

 

[haidut]

I'm not sure about this product.

One user on longecity said it caused him anxiety.

And it is far more economical to give my rats LSD or cheaper derivatives.

Well, I don't expect it to work on all rats. But judging from the experiments on other rats the effects seem to be mostly quite positive.

 

[haidut]

My rat takes quite a high dosage topically (6mg 2x times a day), and feels great. A bit increase in naps taking the first two days. Third day, no naps yet. Overall, I feel very bright and smart, but a bit more lazy than normally. I don't care, because it only allows me to better relax, when I need to relax. Overall productivity in the end of the day is similar (around 3-4 hours of effective study a day in a period of 9 hours).

Definitely increase in sleep quality and morning temperature (orally). Third day morning temperature is 36.6 (was around 35.8-36.2). After lunch temp is 37.6 (was around 37.1-37.3).

First day, after 5 hours taking it, I had a conversation with friends of my parents, telling a bit about my life (my study, the job I get next years etc). I have a bit autistic symptoms (I live with my parents). I'm not good in doing monologue, and speaking a long time about myself. I think I find it hard to focus for so long, and making sentence after sentence.

I was very surprised that I was able to take the time and peace, to just get this thing out, without any problems. After that my mother said she noticed it as well (she didn't know I was on ritanserin). She said that normally she would make sure to be around, when I have such a conversation, to help me formulate the things I want to tell. But she heard me talk to those friends in the garden, and she was very surprised that I could speak with such clarity and confidence, and she didn't felt the need to be around.

I found this a very interesting immediate improvement.

Thanks, this is great feedback!

 

[skycop00]

Beautiful, thank you!

 

[johnwester130]

@haidut


"Ritanserin might be good for some people, but, for me it increased anxiety. It has a long half life and instigated some panic attacks in me and mental disorganization. This is probably due to the fact that I already have anxiety, underlying schizo type symptoms , and, happen to be pretty sensitive to dopaminergics. Ritanserin has a dopaminergic component to it- acts as a DARI. For some this could work for dysthymia, perhaps. I wouldn't recommend it based on my experience."

Interesting... I wonder what is at play here. Of course we don't know his dose or diet. I do get anxiety/panic from macuna puriens which increases dopamine. Maybe @haidut knows. But like most pharma drugs and supplements they are all person specific. Throughout my life 90% of supps I've used haven't really given me an effect I can truly say was positive.

I am looking forward to trying Ritanserin.

mucuna pruriens may deplete tyrosine and phenylalaine

maybe ritanserin does too

 

[haidut]

mucuna pruriens may deplete tyrosine and phenylalaine

maybe ritanserin does too

No it does not, otherwise it would not have had its well-documented dopaminergic effects.

 

[haidut]

I'm not sure about this product.

One user on longecity said it caused him anxiety.

And it is far more economical to give my rats LSD or cheaper derivatives.

Ritanserin is not comparable to LSD. It also happend to be much more legal then LSD. And if you are looking for serotonin antagonism (with some pro-dopamine effects as well) LSD does not even come close to ritanserin. LSD is primarily a hallucinogenic drug with mixed dopamine-serotonin effects. While beneficial for "mental" issues I would not use LSD or its derivative bromocriptine on anybody with fibrosis issues due to the well-documented (partial) serotonergic effects of both. Ritanserin can actually reverse these fibrotic side effects and prevent them when co-administered with either drug. So, there are legitimate uses of both LSD and ritanserin but to say one is just as good as the other is incorrect and at best compares apples to oranges.
Just my 2c.

 

[acrylic]

I know, the fluorine bothered me as well but I could not find any reports of liver or thyroid toxicity. It is the chlorine atoms in second-generation antihistamines that make them liver-toxic. For the record, even cypro has recorded liver toxicity but not ritanserin. Quite the opposite actually, ritanserin seems to protect the liver, even in cases as serious as cirrhosis.
The protective action of ketanserin against lipopolysaccharide-induced shock in mice is mediated by inhibiting inducible NO synthase expression via... - PubMed - NCBI
5-HT2A receptor antagonists inhibit hepatic stellate cell activation and facilitate apoptosis. - PubMed - NCBI
Effect of 5-HT(2) receptor blockade on cadmium-induced acute toxicity. - PubMed - NCBI
Combined treatment of portal hypertension with ritanserin and propranolol in conscious and unrestrained cirrhotic rats. - PubMed - NCBI
Ritanserin decreases portal pressure in conscious and unrestrained cirrhotic rats. - PubMed - NCBI

Do you know which dosages are associated with liver toxicity in Cypro? Do you think 4mg chronically is safe?

 

[haidut]

Do you know which dosages are associated with liver toxicity in Cypro? Do you think 4mg chronically is safe?

I think the few case studies with cypro causing liver damage was in doses of above 12mg and taken for long time (6+ months).

 

[Parsifal]

Increasing dopamine can also increase adrenaline which might explain why some people report anxiety, right?

 

[Such_Saturation]

This should block LSD in rats, can someone try it please?

 

[haidut]

Increasing dopamine can also increase adrenaline which might explain why some people report anxiety, right?

Yes, that too. Good point.

 

[katiekeen]

Thanks for your great supps Haidut! Any idea when lisuride may be available?

 

[Greg says]

Yes, that too. Good point.

so whats the answer to this. if you want to increase your 'get up and go', motivation and drive how do you increase dopamine but not trigger adrenaline?

 

[Mufasa]

so whats the answer to this. if you want to increase your 'get up and go', motivation and drive how do you increase dopamine but not trigger adrenaline?

Just my 2c, but I think "get up and go" is not really what you should be looking for anyway, I think it may be stress fuelled kind of behaviour. With stress hormones, people feel like they must do something "right now".

At least, in my recovery process, I begin to appreciate the more lazy kind of mindset more and more. More like: "Hey, let's do something in about 15 min. but let's first put some music on, and enjoy this beautiful view."

I'm not sure, maybe in a couple of months, I will get out of this mindset, because I'm further in my "healing" process, but I feel like I'm already more productive than I have ever been (I'm a student), while being somewhat lazy. In the past, I would go like a maniac for a week, and then crash for next week lol. Now, I'm just consistently doing a bit every day. But because I never crash anymore, I'm super consistent, even in the weekends I usually do a bit (just for fun), and in the end, I think I do much more, and I'm more creative and flexible in my solutions. In other words, I can do much more in less time.

 

[lindsay]

@haidut - this might seem like a silly question (since most serotonin is produced in the gut), but would Ritanserin benefit gut-related serotonin issues? Or is it more for brain serotonin? I know the two are linked, but I don't usually feel depressed or experience high "brain" serotonin, but I experience serotonin gut issues (nausea, which sometimes causes sinus headaches) when the weather is overcast or a storm is coming; or I am stressed. The other day it was VERY overcast with heavy clouds and I had a busy workday and this happened. Cypro didn't help. Until the nausea passed, the headache wouldn't pass. The two seem to coincide and I've heard this from a friend who gets migraines. I don't get migraines, but I do get sinus headaches when the weather is bad. I know there is a correlation with weather and serotonin. Do you think Ritanserin would be beneficial for this? I like the appeal of it not causing drowsiness. Thanks!

 

[haidut]

@haidut - this might seem like a silly question (since most serotonin is produced in the gut), but would Ritanserin benefit gut-related serotonin issues? Or is it more for brain serotonin? I know the two are linked, but I don't usually feel depressed or experience high "brain" serotonin, but I experience serotonin gut issues (nausea, which sometimes causes sinus headaches) when the weather is overcast or a storm is coming; or I am stressed. The other day it was VERY overcast with heavy clouds and I had a busy workday and this happened. Cypro didn't help. Until the nausea passed, the headache wouldn't pass. The two seem to coincide and I've heard this from a friend who gets migraines. I don't get migraines, but I do get sinus headaches when the weather is bad. I know there is a correlation with weather and serotonin. Do you think Ritanserin would be beneficial for this? I like the appeal of it not causing drowsiness. Thanks!

Ritanserin, just like cypro, is both a peripheral and central serotonin antagonist. As such, it should have effects on gut issues. That is the reason ritanserin has also been tried on people with IBS and carcinoid syndrome, just like cypro has. Ritanserin even produced weight loss results, which is expected from peripheral serotonin antagonist, as a side effect in small human study. As far as I know there are no serotonin antagonists that target only the brain or only the gut. The serotonin "receptors" are everywhere.
Just my 2c.

 

[haidut]

so whats the answer to this. if you want to increase your 'get up and go', motivation and drive how do you increase dopamine but not trigger adrenaline?

Epinephrine synthesis from dopamine is promoted under stress. So, high dopamine does not necessarily lead to high adrenaline / epinephrine. It's stress that shifts the pathway in that direction. This is probably why people experience stress symptoms from caffeine - i.e. they are under a lot of stress and initially the higher dopamine levels produced by caffeine also lead to higher adrenaline.
Epinephrine - Wikipedia, the free encyclopedia
"...Adrenocorticotropic hormone (ACTH) and the sympathetic nervous system stimulate the synthesis of adrenaline precursors by enhancing the activity of tyrosine hydroxylase and dopamine β-hydroxylase, two key enzymes involved in catecholamine synthesis.[citation needed] ACTH also stimulates the adrenal cortex to release cortisol, which increases the expression of PNMT in chromaffin cells, enhancing adrenaline synthesis. This is most often done in response to stress.[citation needed] The sympathetic nervous system, acting via splanchnic nerves to the adrenal medulla, stimulates the release of adrenaline. Acetylcholine released by preganglionic sympathetic fibers of these nerves acts on nicotinic acetylcholine receptors, causing cell depolarization and an influx of calciumthrough voltage-gated calcium channels. Calcium triggers the exocytosis of chromaffin granules and, thus, the release of adrenaline (and noradrenaline) into the bloodstream.[94]"

 

[Drareg]

Epinephrine synthesis from dopamine is promoted under stress. So, high dopamine does not necessarily lead to high adrenaline / epinephrine. It's stress that shifts the pathway in that direction. This is probably why people experience stress symptoms from caffeine - i.e. they are under a lot of stress and initially the higher dopamine levels produced by caffeine also lead to higher adrenaline.
Epinephrine - Wikipedia, the free encyclopedia
"...Adrenocorticotropic hormone (ACTH) and the sympathetic nervous system stimulate the synthesis of adrenaline precursors by enhancing the activity of tyrosine hydroxylase and dopamine β-hydroxylase, two key enzymes involved in catecholamine synthesis.[citation needed] ACTH also stimulates the adrenal cortex to release cortisol, which increases the expression of PNMT in chromaffin cells, enhancing adrenaline synthesis. This is most often done in response to stress.[citation needed] The sympathetic nervous system, acting via splanchnic nerves to the adrenal medulla, stimulates the release of adrenaline. Acetylcholine released by preganglionic sympathetic fibers of these nerves acts on nicotinic acetylcholine receptors, causing cell depolarization and an influx of calciumthrough voltage-gated calcium channels. Calcium triggers the exocytosis of chromaffin granules and, thus, the release of adrenaline (and noradrenaline) into the bloodstream.[94]"

Any idea how to inhibit this? Taurine,mitolipin?

 

[haidut]

Any idea how to inhibit this? Taurine,mitolipin?

Inhibit what? ACTH? PNMT? The stress response?
Well, avoid stress, like Mufasa hinted. Pregnenolone may lower CRH, which is the starting point of the cascade but ACTH can also be stimulated by estrogen and prolactin. So, vitamin E, aspirin, niacinamide, glycine, calcium, vitamin D, vitamin A, should all help. Anti-serotonin drugs definitely lower ACTH, so that's another option.