Metergoline - Liquid Serotonin Antagonist For Lab/R&D

[Quality]

Hi Orion,
As Ive previously assumed in this thread there is a large probability that lowering serotonin too much will mess with rats their sleep, ofcourse this is dependant on the rat, no rat is the same.
After all, serotonin is a pre-cursor to melatonin the sleep hormone.
Maybe would be a wise thing to give a cortisol lowering supplement to your rat in addition to the metergoline, a cheap effective one is ashwagandha.

 

[Orion]

Hi Orion,
As Ive previously assumed in this thread there is a large probability that lowering serotonin too much will mess with rats their sleep, ofcourse this is dependant on the rat, no rat is the same.
After all, serotonin is a pre-cursor to melatonin the sleep hormone.
Maybe would be a wise thing to give a cortisol lowering supplement to your rat in addition to the metergoline, a cheap effective one is ashwagandha.

Thanks good point, I think working on my liver function should continue to help as well.

 

[denise]

@haidut Any idea when this will be back in stock?

 

[haidut]

@haidut Any idea when this will be back in stock?

Hopefully within 2 weeks. All the vendors we are working with are out of stock and it has to be synthesized from scratch.

 

[Quality]

@Constatine
@Pointless

Any updates on this?
Mine should be arriving either today or tomorrow.

 

[Pointless]

Subject got some downregulation from Lisuride and not too much progress on health goals with a short course of Metergoline, so I discontinued it for now.

 

[Quality]

I see, so you were using metergoline at the same time as lisuride?
That would make it hard to judge its actual effects.
Also, did some form of tollerance set in?

 

[Pointless]

I see, so you were using metergoline at the same time as lisuride?
That would make it hard to judge its actual effects.
Also, did some form of tollerance set in?

Subject stopped the Lisuride as it started on Metergoline. Results aren't very clear so I decided not to post anything on it.

Lisuride OTOH gave subject impotence and weight gain whereas it was the opposite the first few days. 2 drops per day.

 

[Quality]

Subject stopped the Lisuride as it started on Metergoline. Results aren't very clear so I decided not to post anything on it.

Lisuride OTOH gave subject impotence and weight gain whereas it was the opposite the first few days. 2 drops per day.

I suspect this has to do with the 5ht1a agonism of lisuride, which is like a break on sexual behavior.

 

[Pointless]

I suspect this has to do with the 5ht1a agonism of lisuride, which is like a break on sexual behavior.

Yes, I think you're right. I mentioned "downregulation" from Lisuride, but the partial serotonin agonism is a possibility. I really don't know. Also, considering the study that shows Metergoline has no effect on receptor density in the serotonin receptors studied, there's a pretty good chance that Metergoline will not have the same problems that Lisuride had for the subject. Be careful, though.

 

[johnwester130]

Do you know by how much certain substances block serotonin ? Like in a chart or graph comparing certain substances ?

 

[haidut]

Do you know by how much certain substances block serotonin ? Like in a chart or graph comparing certain substances ?

I don't know of such a chart but you can gauge approximate effectiveness based on dosage and also the Km values for the various serotonin receptors. Serotonin antagonists like metergoline, ritanserin, cyproheptadine, ondansetron all block the serotonin receptors in nanomolar concentrations, so they are all pretty effective and similarly so, depending on the receptor they target.

 

[allblues]

Subject has been using this for about 2 weeks, with a small 2 day break last weekend. Subject likes it so far, it feels very mild, compared to lisuride/other ergolines with some serotonin agonism, that produced some jitters.

I've been researching changes to the serotonergic system from SSRI use for a while and metergoline with its specific actions seems like a useful tool, and the subject seems to agree, he's had some really good feels from this, like he remembers it used to be before using SSRIs.

Going off it for two days made the subject feel worse, found this study which predicts possible bad feels;
Withdrawal from chronic treatment with metergoline, dl-propranolol and amitriptyline enhances serotonin receptor mediated behaviour in the rat

The withdrawal was eased pretty OK with a small dose of cyproheptadine.
Still unsure about how many days straight to take this. Subject wants to try to follow Rays advice not to use these types of compounds for too long. Homeostasis is a thing.

Also found this which seems logical enough, antagonizing 5HT with MET increases 5HT binding sites (= upregulates receptors i guess), while an 5HT release + uptake inhibiting agent caused a lowered amount of 5HT binding sites.
Repeated treatment with d-fenfluramine or metergoline alters cortex binding of 3H-serotonin and serotonergic sensitivity in rats

So there's a direct reverse effect of MET as compared to an SSRI. If SERT function is still compromised, this still might not be a complete answer to the problem, but so far so good.

 

[InChristAlone]

Someone had to be the bigger man

Whoa sorry you got treated that way! No way don't do benzos or SSRI's.

 

[Quality]

Subject has been using this for about 2 weeks, with a small 2 day break last weekend. Subject likes it so far, it feels very mild, compared to lisuride/other ergolines with some serotonin agonism, that produced some jitters.

I've been researching changes to the serotonergic system from SSRI use for a while and metergoline with its specific actions seems like a useful tool, and the subject seems to agree, he's had some really good feels from this, like he remembers it used to be before using SSRIs.

Going off it for two days made the subject feel worse, found this study which predicts possible bad feels;
Withdrawal from chronic treatment with metergoline, dl-propranolol and amitriptyline enhances serotonin receptor mediated behaviour in the rat

The withdrawal was eased pretty OK with a small dose of cyproheptadine.
Still unsure about how many days straight to take this. Subject wants to try to follow Rays advice not to use these types of compounds for too long. Homeostasis is a thing.

Also found this which seems logical enough, antagonizing 5HT with MET increases 5HT binding sites (= upregulates receptors i guess), while an 5HT release + uptake inhibiting agent caused a lowered amount of 5HT binding sites.
Repeated treatment with d-fenfluramine or metergoline alters cortex binding of 3H-serotonin and serotonergic sensitivity in rats

So there's a direct reverse effect of MET as compared to an SSRI. If SERT function is still compromised, this still might not be a complete answer to the problem, but so far so good.

Interesting,
How do you feel it impacted your mood while on it, everything became more intense? any feelings of aggression?
You said you felt 'worse' while off it, enlighten us? dulled? anhedonic?
Also how was your dosing, and at what time of the day? Did you experience sleeping issues?

My metergoline arrived yesterday at my house, I will have a washout of ALL my supplements for 2 weeks to get everything out of my system so I can test this substance standalone.

 

[haidut]

Subject has been using this for about 2 weeks, with a small 2 day break last weekend. Subject likes it so far, it feels very mild, compared to lisuride/other ergolines with some serotonin agonism, that produced some jitters.

I've been researching changes to the serotonergic system from SSRI use for a while and metergoline with its specific actions seems like a useful tool, and the subject seems to agree, he's had some really good feels from this, like he remembers it used to be before using SSRIs.

Going off it for two days made the subject feel worse, found this study which predicts possible bad feels;
Withdrawal from chronic treatment with metergoline, dl-propranolol and amitriptyline enhances serotonin receptor mediated behaviour in the rat

The withdrawal was eased pretty OK with a small dose of cyproheptadine.
Still unsure about how many days straight to take this. Subject wants to try to follow Rays advice not to use these types of compounds for too long. Homeostasis is a thing.

Also found this which seems logical enough, antagonizing 5HT with MET increases 5HT binding sites (= upregulates receptors i guess), while an 5HT release + uptake inhibiting agent caused a lowered amount of 5HT binding sites.
Repeated treatment with d-fenfluramine or metergoline alters cortex binding of 3H-serotonin and serotonergic sensitivity in rats

So there's a direct reverse effect of MET as compared to an SSRI. If SERT function is still compromised, this still might not be a complete answer to the problem, but so far so good.

Btw, higher receptor density/sensitivity is usually not a bad thing.

 

[allblues]

@Quality Yeah, subject feels that life is more intense, in a good way. He's often been very passive these last few years, MET has brought back feelings of activity and aggression in the sense of "not always avoiding conflicts/tense situations of all sorts."
This is a very nice thing and makes life much richer, subject hopes he can continue on this track.

Oh, and situations which usually have seemed "tense" and impossible to handle now more often
feel fun and intriguing, discussions with others, talking to strangers, for example.

The two off-days brought on what the subject thinks was 5HT-rebound, dull feelings, slight paranoia, tense. This used to be pretty common, but has been milder the past year. Dealing with people/world seemed difficult.

Oh yeah forgot dosing, subject has been using 4 drops @ morning. No sleeping issues so far.

Another cool thing was vision improvement at the full 8 drops. Subject was walking outside on an autumn days with 8 drops in the system and the trees and leaves were just crazy crisp. Haven't seen (heh) noticable difference at the 4 drops for vision.

@haidut Thanks again for making the stuff available. Yeah, that's what i've been seeing as well, aging, generalized stress etc reducing receptor density/sensitivity. Stress-induced 5-HT1A receptor desensitization: protective effects of Ginkgo biloba extract (EGb 761). - PubMed - NCBI

A dilemma for a person with defective/low serotonin transporter function,
antagonized and downregulated by SSRIs, could be that increased receptor sensitivity will bring on a more difficult situation when you quit serotonin antagonists, 5HT rebounds and you haven't regained ability to deal with the 5HT through the SERT.

Which could then just redo the whole process of overexposure, downregulation. But that's half-speculation.
There's more to the story about MET being helpful with the quite unique 5HT1A antagonism, i might post a thread on that stuff later.

By the way, there's some really cool research being done on SERT-knockout mice, anyone interested could search "SERT knockout" or such on Pubmed.
There's plenty of gathering information about how antagonizing the seemingly very important serotonin binding protein could be bad news in a number of ways.

 

[Quality]

Thanks, this is great feedback!
Btw, higher receptor density/sensitivity is usually not a bad thing.

Hopefully.
Serotonin is so complex, but there might be a chance that metergoline would make people more sensitive to the effects of psychedelics and MDMA, which might make it of some use for people going through withdrawal of those.

Generally speaking I think serotonin is a bad thing to most of us, I ALWAYS use BCAA before, during and shortly after HIIT and lifting, it has a very strong energizing effect on me.
Besides that it feels like a metobolic switch, after and intense workout without BCAA I feel drained (serotonin rising for sure and possibly cortisol going up alot), this effect feels completely abolished when using BCAA's and I get an intense energy burst after a workout for 3-4hours long.

 

[Quality]

@Quality Yeah, subject feels that life is more intense, in a good way. He's often been very passive these last few years, MET has brought back feelings of activity and aggression in the sense of "not always avoiding conflicts/tense situations of all sorts."
This is a very nice thing and makes life much richer, subject hopes he can continue on this track.

Oh, and situations which usually have seemed "tense" and impossible to handle now more often
feel fun and intriguing, discussions with others, talking to strangers, for example.

The two off-days brought on what the subject thinks was 5HT-rebound, dull feelings, slight paranoia, tense. This used to be pretty common, but has been milder the past year. Dealing with people/world seemed difficult.

Oh yeah forgot dosing, subject has been using 4 drops @ morning. No sleeping issues so far.

Another cool thing was vision improvement at the full 8 drops. Subject was walking outside on an autumn days with 8 drops in the system and the trees and leaves were just crazy crisp. Haven't seen (heh) noticable difference at the 4 drops for vision.

@haidut Thanks again for making the stuff available. Yeah, that's what i've been seeing as well, aging, generalized stress etc reducing receptor density/sensitivity. Stress-induced 5-HT1A receptor desensitization: protective effects of Ginkgo biloba extract (EGb 761). - PubMed - NCBI

A dilemma for a person with defective/low serotonin transporter function,
antagonized and downregulated by SSRIs, could be that increased receptor sensitivity will bring on a more difficult situation when you quit serotonin antagonists, 5HT rebounds and you haven't regained ability to deal with the 5HT through the SERT.

Which could then just redo the whole process of overexposure, downregulation. But that's half-speculation.
There's more to the story about MET being helpful with the quite unique 5HT1A antagonism, i might post a thread on that stuff later.

By the way, there's some really cool research being done on SERT-knockout mice, anyone interested could search "SERT knockout" or such on Pubmed.
There's plenty of gathering information about how antagonizing the seemingly very important serotonin binding protein could be bad news in a number of ways.

My theory( and I will put it to the best ), will involve low/ultra low dose of metergoline, just enough to antagonize the autoreceptor and basically forcing the 5ht1a autoreceptor to upregulate in a state as it was BEFORE antidepressant use.
Hopefully this might be a long term SUSTAINABLE approach, also the dose might be VERY important and timing.
Initially it might make symptoms worse but once the brain starts compensating by increasing its 5ht1a autoreceptors improvement might happen.

Double-blind, placebo-controlled study of single-dose metergoline in depressed patients with seasonal affective disorder

Double-blind, placebo-controlled study of single-dose metergoline in depressed patients with seasonal affective disorder. - PubMed - NCBI

Sixteen untreated, depressed patients with SAD received single oral doses of metergoline 8 mg and of placebo, spaced 1 week apart.

Patient daily self-ratings suggested that the peak effect occurred 2 to 4 days after study drug administration!!!


2-4 days after these people taking a single dose of 8mg, that would mean the drug would be nearly completely if not completely out of their system (metergoline has a half life of 12hours).

So the improvement these people were getting was not from the antagonizing effect of metergoline itself, but rather from the compensation mechanism the brain gives by cleaning it out of your system?

edit: forgot to add, I have used that specific ginkgo biloba extract in the past (Natures Way Ginkgold, which is EGB761), it actually gave me closed eye hallucinations @120mg/day the first 2 days combined with a low dose ashwagandha.
Had to stop it though, it gave me increase intraocular pressure (ginkgo is a blood thinner, and there have been cases of people getting internal bleedings in their brain) and ginkgo should be classed as a drug to be honest, EGB761 is a prescription drug here in holland.

 

[allblues]

That's really cool, my subject actually did a one-day trial first. He did have a mood lift a few days later and wondered what that was.
Will you (your subject/pink elephant) be trying it that way to start?