haidut

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This chemical metergoline is a very interesting substance and is a continuation of my search for chemicals that combine several beneficial characteristics into a single molecule/entity. Metergoline belongs to the same class of drugs as bromocriptine, lisuride, cabergoline, terguride, etc. However, unlike them it is an antagonist at the serotonin receptors 5-HT1, 5-HT2, 5-HT6, and 5-HT7. Most ergot drugs are agonists on those receptors with the possible (and partial) exception of lisuride. More importantly, just like lisuride metergoline is an antagonist at the dreaded 5-HT2B receptor. This may endow it with anti-fibrotic properties similar to lisuride, terguride, ritanserin and cyproheptadine. In addition, unlike other serotonin antagonist that simply block serotonin receptors metergoline is actually capable of also reducing serotonin synthesis. The putative dopamine agonism is probably responsible at least partially for this effect. Furthermore, metergoline has been shown to lower prolactin in humans and animal models, with effectiveness similar to bromocriptine when used in the same doses. Preliminary research suggests that metergoline is an agonist at the D2 receptor, which is not surprising given its similarity to lisuride, bromocriptine, etc. However, its exact dopamine receptor agonism profile is not well-known. What is even more interesting is that metergoline is capable of lowering prolactin through a (currently unknown) non-dopaminergic mechanism. So, it represents a viable alternative with less risk for dopamine receptor downregulation.
Some other interesting properties (according to the published studies) include ability to lower cortisol in doses as low as 2mg daily, improve insulin sensitivity in animal models, and act as an antidepressant.
Finally, metergoline possesses activity against the Candida strain of fungi and especially the potentially lethal strain Candida krusei, which typically kills 50% - 60% of the people it infects and is naturally resistant to antifungals like fluconazole. As far as I know, metergoline is unique among all ergot derivatives in its anti-fungal properties.

Metergoline - Wikipedia, the free encyclopedia
metergoline (CHEBI:64216)
metergoline
"...Summary: A dopamine agonist and serotonin antagonist. It has been used similarly to BROMOCRIPTINE as a dopamine agonist and also for MIGRAINE DISORDERS therapy."

The units listed on the label are based on the studies that used metergoline in human and animal studies. In general, doses of metergoline found to have clinically meaningful effect are virtually the same as the doses for bromocriptine, which is in the range of 2mg - 4mg daily. Please note that similar to the products sold by companies like BluePeptides, this product if for lab/research use only. The product can be ordered from the link below:
www.idealabsdc.com/lab

*******************************************************************************
Metergoline is a non-selective serotonin antagonist and putative dopamine agonist. As a serotonin antagonist it targets the 5-HT1, 5-HT2, 5-HT6, and 5-HT7 receptors but due to its general antiserotonin effects it is considered a non-specific serotonin antagonist similar to cyproheptadine. The dopamine agonism profile of metergoline is not well-known except some evidence for D2 receptor agonism. Metergoline is capable of lowering prolactin through both dopaminergic and non-dopaminergic mechanisms and displays similar effectiveness to bromocriptine in the same dose range, and the two drugs are considered synergistic. One of the most interesting properties of metergoline is its antifungal activity against Candida strains, which are naturally resistant to anti-fungal drugs.

Drops per container: about 250
Each drop contains the following ingredients:

Metergoline: 0.45 mg

Other ingredients: add product to shopping cart to see info
*******************************************************************************

References:

Miscellaneous
https://www.ncbi.nlm.nih.gov/pubmed/24909513
The effects of metergoline and 8-OH-DPAT injections into arcuate nucleus and lateral hypothalamic area on feeding in female rats during the estrous... - PubMed - NCBI
Serotonin antagonist-induced lowering of prolactin secretion does not affect the pattern of pulsatile secretion of follicle-stimulating hormone and... - PubMed - NCBI
Serotoninergic modulation of sodium appetite in the rat. - PubMed - NCBI
Further evidence for an inhibitory role of central 5-HT in male rat sexual behavior. - PubMed - NCBI


Neurological/Brain
https://www.ncbi.nlm.nih.gov/pubmed/16921395
Naloxone and metergoline effects on growth hormone response to gamma-hydroxybutyric acid. - PubMed - NCBI
The effects of metergoline combined with PGF2alpha treatment on luteal function and gestation in pregnant ********. - PubMed - NCBI
Stimulation of serotonin1A receptors increases release of prolactin in the rat. - PubMed - NCBI
Does metergoline selectively attenuate 5-HT mediated prolactin release? - PubMed - NCBI
Metergoline abolishes the prolactin response to buspirone. - PubMed - NCBI
Activation of 5-HT 1 serotonin receptors in the medial basal hypothalamus stimulates prolactin secretion in the unanaesthetized rat. - PubMed - NCBI
Metergoline as an inhibitor of prolactin release. - PubMed - NCBI
The effect of metergoline on endocrine responses to L-tryptophan. - PubMed - NCBI
The behavioural effects of intravenously administered tryptamine in mice. - PubMed - NCBI
Serotonin initiates and autoamplifies its own synthesis during mouse central nervous system development. - PubMed - NCBI
Treatment of hyperprolactinemic amenorrhea with Metergoline. - PubMed - NCBI
Metergoline, pirenperone and pizotifen alter dopamine and 5-hydroxytryptamine synthesis in discrete rat brain nuclei. - PubMed - NCBI
Intolerance of bromocriptine: is metergoline a satisfactory alternative? - PubMed - NCBI
Metergoline as an alternative to bromocriptine in amenorrhoea. - PubMed - NCBI
Effect of metergoline on prolactin, follicle stimulating hormone, luteinizing hormone and thyroid stimulating hormone response to TRH and LHRH in n... - PubMed - NCBI
Treatment of hyperprolactinaemia with metergoline for periods up to 5 years: clinical and biological tolerability. - PubMed - NCBI
Metergoline as a lactation inhibitor. - PubMed - NCBI
Treatment of hyperprolactinemic states with different drugs: a study with bromocriptine, metergoline, and lisuride. - PubMed - NCBI
Metergoline and cyproheptadine suppress prolactin release by a non-5-hydroxytryptaminergic, non-dopaminergic mechanism. - PubMed - NCBI
Effect of metergoline on serum prolactin stimulated by TRH. - PubMed - NCBI
Prolactin suppression by serotonin antagonists in man: further evidence for serotoninergic control of prolactin secretion. - PubMed - NCBI
Growth hormone and prolactin release in acromegalic patients following metergoline administration. - PubMed - NCBI

https://www.ncbi.nlm.nih.gov/pubmed/3924253
"...As metergoline acts predominantly as a serotonin antagonist it might be expected to have additive or synergistic effects when combiend with bromocriptine. Although it has some dopaminergic activity, this is probably not the mechanism that suppressed prolactin. Interestingly, the prolactin concentration in one patient was reduced further when 2.5mg bromocriptine was added to treatment...Metergoline provides satisfactory treatment for many patients unable to tolerate bromocriptine and should beuseful in the management of hyperprolactinaemia either alone or combined with a small dose of bromocriptine."

https://www.ncbi.nlm.nih.gov/pubmed/662027 (MET decreases serotonin synthesis as well)
Metergoline inhibition of thyrotrophin and prolactin secretions in primary hypothyroidism. - PubMed - NCBI (prometabolic - lowers TRH)

Mood/Cognition/Behavior/Addiction
https://www.ncbi.nlm.nih.gov/pubmed/11910270
Regulation of Human Kv1.4 Channel Activity by the Antidepressant Metergoline. - PubMed - NCBI
Cocaine modulates mammalian circadian clock timing by decreasing serotonin transport in the SCN. - PubMed - NCBI
An investigation into the effects of 5-HT agonists and receptor antagonists on ethanol self-administration in the rat. - PubMed - NCBI
Metergoline antagonizes fluoxetine-induced suppression of food intake but not changes in the behavioural satiety sequence. - PubMed - NCBI
Metergoline potentiates natural feeding and antagonizes the anorectic action of medical hypothalamic 5-hydroxytryptamine. - PubMed - NCBI
Effects of 5-HT receptor antagonists on morphine-induced tolerance in mice. - PubMed - NCBI
Effects of serotonin and the serotonin blocker metergoline on meal patterns and macronutrient selection. - PubMed - NCBI
Partial reversal of fluoxetine anorexia by the 5-HT antagonist metergoline. - PubMed - NCBI
Metergoline blocks the behavioral and neuroendocrine effects of orally administered m-chlorophenylpiperazine in patients with obsessive-compulsive ... - PubMed - NCBI
Dopaminergic mechanism of imipramine action in an animal model of depression. - PubMed - NCBI
Increased food intake and carbohydrate preference in the rat following treatment with the serotonin antagonist metergoline. - PubMed - NCBI
Animal model of anxiety: effect of metergoline in the genetically hypertensive rats of Koletsky type and in the rats of Wistar strain. - PubMed - NCBI
Increased food intake in satiated rats induced by the 5-HT antagonists methysergide, metergoline and ritanserin. - PubMed - NCBI
Serotonergic modulation of yawning. - PubMed - NCBI


CVD/Circulation/Hypertension/Calcification
https://www.ncbi.nlm.nih.gov/pubmed/2412045
Effect of metergoline on the aldosterone-stimulating properties of metoclopramide. - PubMed - NCBI
Pharmacological evidence that stimulation of central serotonergic pathways increases renin secretion. - PubMed - NCBI


Fibrosis/Cancer
https://www.ncbi.nlm.nih.gov/pubmed/7805767
Nicotine stimulates a serotonergic autocrine loop in human small-cell lung carcinoma. - PubMed - NCBI
[Metergoline in hyperprolactinemic breast cancer: a phase II study]. - PubMed - NCBI


Metabolism/Diabetes/Cortisol/Insulin/Obesity
https://www.ncbi.nlm.nih.gov/pubmed/499287
The effects of metergoline and other serotonin receptor antagonists on serum corticosterone in rats. - PubMed - NCBI
Serotonin mediated changes in corticotropin releasing factor mRNA expression and feeding behavior isolated to the hypothalamic paraventricular nuclei. - PubMed - NCBI
Effects of the non-selective 5-HT receptor agonist, 5-carboxamidotryptamine, on plasma glucose levels in rats. - PubMed - NCBI
Effect of selective serotonin agonists on basal, corticotrophin-releasing hormone- and vasopressin-induced ACTH release in vitro from rat pituitary... - PubMed - NCBI
Stimulation of the hypothalamo-pituitary-adrenocortical axis by the central serotonergic pathway: involvement of endogenous corticotropin-releasing... - PubMed - NCBI
Effects of serotonergic agonists and antagonists on corticotropin-releasing hormone secretion by explanted rat hypothalami. - PubMed - NCBI
Stimulation of corticosterone and beta-endorphin secretion in the rat by selective 5-HT receptor subtype activation. - PubMed - NCBI
Effect of an antiserotoninergic drug, metergoline, on the ACTH and cortisol response to insulin hypoglycemia and lysine-vasopressin in man. - PubMed - NCBI
Effect of metergoline, a powerful and long-acting antiserotoninergic agent, on insulin secretion in normal subjects and in patients with chemical d... - PubMed - NCBI

Digestion/GI
https://www.ncbi.nlm.nih.gov/pubmed/17965538
Serotonin inhibits gastric acid secretion through a 5-hydroxytryptamine1-like receptor in the rat. - PubMed - NCBI


Immune/Antirival/Antibacterial/Antiparasitic
https://www.ncbi.nlm.nih.gov/pubmed/21354537
In vitro synergistic effects of metergoline and antifungal agents against Candida krusei. - PubMed - NCBI
http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004063
 
Last edited:

haidut

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Just wanted to say that the first batch we have is limited, so please don't get mad if we run out over the weekend :): There is a federal holiday on Monday in the USA and that can delay shipments. Doing our best to avoid interruptions but just wanted to let people know. Thanks for the understanding.
 

aarfai

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Thank you haidut! Do you know the half-life and binding affinity toward the 5-HT1, 5-HT2, 5-HT6, and 5-HT7 receptors? I couldn't find much info on it.
 
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allblues

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I just ordered, hope there's still a few bottles left ;)
Really something special to get access to a 5ht1-antagonist, which metergoline seems to be, at least of the A, B and D varieties.
This is really exciting. Thank you @haidut.

Maybe haidut has a better overview of this but here's some of the binding properties;
According to this it's as potent as LSD at the 5ht1-receptor (family?), but apparently then as an antagonist;
Biochemical Immunological Pharmacology
 

haidut

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Thank you haidut! Do you know the half-life and binding affinity toward the 5-HT1, 5-HT2, 5-HT6, and 5-HT7 receptors? I couldn't find much info on it.

The half-life seems rather long - about 12h, so it can be administered only twice a day and in fact most studies I saw used once daily administration.
Small Animal Clinical Pharmacology

Will find the binding affinity and post here later tonight.
 

haidut

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I just ordered, hope there's still a few bottles left ;)
Really something special to get access to a 5ht1-antagonist, which metergoline seems to be, at least of the A, B and D varieties.
This is really exciting. Thank you @haidut.

Maybe haidut has a better overview of this but here's some of the binding properties;
According to this it's as potent as LSD at the 5ht1-receptor (family?), but apparently then as an antagonist;
Biochemical Immunological Pharmacology

Oh, perfect! Thanks for posting this. I was about to go dig into my sources. Still have to find the studies that talk about 5-HT6 and 5-HT7 affinity but most people probably don't care about those receptors.
Metergoline is a very rare find indeed. A purely antiserotonin ergot is virtually unheard of and this chemical was harder to obtain than even ritanserin.
 

CaseyL

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Is the anti-fungal action based on in vitro experiments where it was applied in high concentrations to a culture, or was it utilized to resolve actual infections in vivo? I'm curious as to whether the doses of 2-4mg a day would have a meaningful effect on Candida or other fungal infections.

Also, would there be a preferred route of administration to combat fungal infections; say oral for GI tract, or directly on an affected area of the skin?

Thanks!
 

allblues

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You might wanna preorder one of these popehat.jpg, in case this happens to be helpful for the dreaded post-SSRI, or general serotonergic sexual dysfunction, there's every chance you will be proclaimed our first Saint.
Jokes aside, thanks again for making this avaliable, the already unique Idealabs just got a little more unique.
 

allblues

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Holy smokes! Order shipped! Let me just bow down a few times on my Washington-directed carpet.
 

haidut

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You might wanna preorder one of these View attachment 3616, in case this happens to be helpful for the dreaded post-SSRI, or general serotonergic sexual dysfunction, there's every chance you will be proclaimed our first Saint.
Jokes aside, thanks again for making this avaliable, the already unique Idealabs just got a little more unique.

Lol, thanks. I can settle for the title "rogue nutritionist". Sort of like gastronomical "haidut" :):
 

haidut

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I fail to see how this differs from lisuride or even ritanserin

There are certainly parallels with ritanserin but it is very different in terms of action from lisuride. Ritanserin is also a non-specific serotonin antagonist but its pro-dopamine effects are through a slight dopamine reuptake inhibition. Metergoline is an actual D2 agonist, similar to bromo and lisuride. Lisuride is a full agonist on the entire dopamine receptor suite D1 through D5 and metergoline is known to only agonize D2. So, it is very likely a much weaker dopamine agonist than lisuride. Also, lisuride is actualy a serotonin agonist on 5-HT1, 5-HTA/C and maybe even 5-HT6.
 
Last edited:

DaveFoster

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This seems like a very interesting substance, (I assume the dopamine agonist/serotonin antagonist that you mentioned.) However, it sounds preliminary in its research and risky for use on mammals outside of rats, at the very least in the long-term.
 

haidut

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This seems like a very interesting substance, (I assume the dopamine agonist/serotonin antagonist that you mentioned.) However, it sounds preliminary in its research and risky for use on mammals outside of rats, at the very least in the long-term.

Metergoline is actually one of the safest (if not THE safest) ergot derivative. It has been in use for decades and is approved as a migraine and Parkinson drug in many countries (EU and Asia mostly) even though it is not in wide use due to the very high cost of production.
 
Last edited:

DaveFoster

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Metergoline is actually one of the safest (if not THE safest) ergot derivative. It has been in use for decades and is approved as a migraine and Parkinson drug in many countries (EU and Asia mostly) even though it is not in wide use due to the very high cost of production. It is considered the mildest ergot derivative in clinical or research use. So, untested experimental about it :)
Interesting; thanks for clarifying.

However, its exact dopamine receptor agonism profile is not well-known. What is even more interesting is that metergolilne is capable of lowering prolactin through a (currently unknown) non-dopaminergic mechanism.
This made me think otherwise; there's a typo by the way, just noticed.
 

haidut

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Interesting; thanks for clarifying.

This made me think otherwise; there's a typo by the way, just noticed.

Fixed the typos, thanks for noticing them.
 

BobbyDukes

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With odansetron being a 5ht3 antagonist, does this mean that this compound may lack the problems some experience with constipation? I don't see 5ht3 mentioned, and a Google search doesn't show anything (unless I've missed it). That is the only problem I got from ritanserin/odansetron. Cypro, in very small dosages, promoted regularity.

As for lisuride, I've hardly touched that bottle as couldn't handle the nausea.

Here in England; What with the Pound falling on its backside; Your supplements are now becoming more expensive :-( ... So I will save up for this one :))
 

haidut

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With odansetron being a 5ht3 antagonist, does this mean that this compound may lack the problems some experience with constipation? I don't see 5ht3 mentioned, and a Google search doesn't show anything (unless I've missed it). That is the only problem I got from ritanserin/odansetron. Cypro, in very small dosages, promoted regularity.

As for lisuride, I've hardly touched that bottle as couldn't handle the nausea.

Here in England; What with the Pound falling on its backside; Your supplements are now becoming more expensive :-( ... So I will save up for this one :))

Yes, that is one of the nicer things about metergoline - it does not seem to have activity on 5-HT3 and thus does not cause constipation. So, due to this lack of constipating activity it is used in some countries off-label to treat both IBS-C and IBS-D.
 

BobbyDukes

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Yes, that is one of the nicer things about metergoline - it does not seem to have activity on 5-HT3 and thus does not cause constipation. So, due to this lack of constipating activity it is used in some countries off-label to treat both IBS-C and IBS-D.

I couldn't find much on ritanserin and 5ht3, either. Does this mean that ritanserin may cause constipation from a different mechanism? Saying that, I'm only going from my own experience with it, and one or two others who posted in the thread. We may be lone cases. Or it may be weak at that receptor, and the DMSO just makes it strong enough to cause that side effect.

I will watch this thread with interest :)
 

Constatine

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Amazing substance. It would be interesting to see some experience reports. Have you personally used this substance Haidut?
 
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