1. 10% Discount At RedLightMan.com For Ray Peat Forum Members!
    Click Here For More Information
    Dismiss Notice

Metergoline - Serotonin Antagonist & Dopamine Agonist For R&D

Discussion in 'IdeaLabs' started by haidut, Oct 7, 2016.

  1. haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    9,985
    Gender:
    Male
    Location:
    USA / Europe
    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 a potent antagonist on 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 a potent antagonist on the dreaded 5-HT2B receptor. This endows 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 consistently 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 for experiments where lowering of prolactin is desirable but WITHOUT agonism (and potential downregulation) of dopamine receptors.
    Some other interesting properties include ability to lower cortisol in doses as low as 2mg daily, improve insulin sensitivity in animal models, and act as a potent antidepressant in humans.
    Finally, metergoline possesses potent 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. In fact, both chemicals can be used together for an even more potent effect. Other dopamine agonists such as lisuride also synergize greatly with metergoline. However, 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 potent 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 just like 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.

    Units per container: about 30
    Unit size: 8 drops
    Each unit contains the following ingredients:

    Metergoline: 3.3 mg

    Other ingredients: DMSO, ethanol
    *******************************************************************************

    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
    https://www.ncbi.nlm.nih.gov/pubmed/662080
    https://www.ncbi.nlm.nih.gov/pubmed/1002821

    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)
    https://www.ncbi.nlm.nih.gov/pubmed/627092 (prometabolic - lowers TRH)

    Mood/Cognition/Behavior/Addiction
    https://www.ncbi.nlm.nih.gov/pubmed/11910270
    https://www.ncbi.nlm.nih.gov/pubmed/27251511
    https://www.ncbi.nlm.nih.gov/pubmed/24950119
    https://www.ncbi.nlm.nih.gov/pubmed/9744857
    https://www.ncbi.nlm.nih.gov/pubmed/8853199
    https://www.ncbi.nlm.nih.gov/pubmed/8801574
    https://www.ncbi.nlm.nih.gov/pubmed/7737326
    https://www.ncbi.nlm.nih.gov/pubmed/8516357
    https://www.ncbi.nlm.nih.gov/pubmed/1615137
    https://www.ncbi.nlm.nih.gov/pubmed/2018816
    https://www.ncbi.nlm.nih.gov/pubmed/2378927
    https://www.ncbi.nlm.nih.gov/pubmed/2812508
    https://www.ncbi.nlm.nih.gov/pubmed/2799267
    https://www.ncbi.nlm.nih.gov/pubmed/3148151
    https://www.ncbi.nlm.nih.gov/pubmed/504319


    CVD/Circulation/Hypertension/Calcification
    https://www.ncbi.nlm.nih.gov/pubmed/2412045
    https://www.ncbi.nlm.nih.gov/pubmed/6350721
    https://www.ncbi.nlm.nih.gov/pubmed/6986577


    Fibrosis/Cancer
    https://www.ncbi.nlm.nih.gov/pubmed/7805767
    https://www.ncbi.nlm.nih.gov/pubmed/8221698
    https://www.ncbi.nlm.nih.gov/pubmed/3101016


    Metabolism/Diabetes/Cortisol/Insulin/Obesity
    https://www.ncbi.nlm.nih.gov/pubmed/499287
    https://www.ncbi.nlm.nih.gov/pubmed/477605
    https://www.ncbi.nlm.nih.gov/pubmed/21600959
    https://www.ncbi.nlm.nih.gov/pubmed/9831297
    https://www.ncbi.nlm.nih.gov/pubmed/8386213
    https://www.ncbi.nlm.nih.gov/pubmed/1658112
    https://www.ncbi.nlm.nih.gov/pubmed/2787501
    https://www.ncbi.nlm.nih.gov/pubmed/2956114
    https://www.ncbi.nlm.nih.gov/pubmed/181396
    https://www.ncbi.nlm.nih.gov/pubmed/1149950

    Digestion/GI
    https://www.ncbi.nlm.nih.gov/pubmed/17965538
    https://www.ncbi.nlm.nih.gov/pubmed/7932163


    Immune/Antirival/Antibacterial/Antiparasitic
    https://www.ncbi.nlm.nih.gov/pubmed/21354537
    https://www.ncbi.nlm.nih.gov/pubmed/19538518
    http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004063
     
  2. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    9,985
    Gender:
    Male
    Location:
    USA / Europe
    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.
     
  3. aarfai

    aarfai Member

    Joined:
    Oct 16, 2015
    Messages:
    100
    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.
     
  4. allblues

    allblues Member

    Joined:
    Oct 30, 2015
    Messages:
    175
    Gender:
    Male
    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
     
  5. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    9,985
    Gender:
    Male
    Location:
    USA / Europe
    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.
     
  6. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    9,985
    Gender:
    Male
    Location:
    USA / Europe
    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.
     
  7. CaseyL

    CaseyL Member

    Joined:
    Sep 16, 2014
    Messages:
    7
    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!
     
  8. allblues

    allblues Member

    Joined:
    Oct 30, 2015
    Messages:
    175
    Gender:
    Male
    You might wanna preorder one of thesepopehat.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.
     
  9. allblues

    allblues Member

    Joined:
    Oct 30, 2015
    Messages:
    175
    Gender:
    Male
    Holy smokes! Order shipped! Let me just bow down a few times on my Washington-directed carpet.
     
  10. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    9,985
    Gender:
    Male
    Location:
    USA / Europe
    Lol, thanks. I can settle for the title "rogue nutritionist". Sort of like gastronomical "haidut" :)
     
  11. johnwester130

    johnwester130 Member

    Joined:
    Aug 6, 2015
    Messages:
    936
    I fail to see how this differs from lisuride or even ritanserin
     
  12. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    9,985
    Gender:
    Male
    Location:
    USA / Europe
    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. IMO, metergoline represents a sort of a compromise for rats that cannot take both a serotonin antagonist and dopamine agonist. If only one chemical has to be used to achieve both effects, metergoline is a decent option and can always be made more dopaminergic by adding a dopamine agonist like lisuride.
     
  13. DaveFoster

    DaveFoster Member

    Joined:
    Jul 23, 2015
    Messages:
    3,190
    Gender:
    Male
    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.
     
  14. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    9,985
    Gender:
    Male
    Location:
    USA / Europe
    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, nothing untested about it :)
     
  15. DaveFoster

    DaveFoster Member

    Joined:
    Jul 23, 2015
    Messages:
    3,190
    Gender:
    Male
    Interesting; thanks for clarifying.

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

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    9,985
    Gender:
    Male
    Location:
    USA / Europe
    Fixed the typos, thanks for noticing them.
     
  17. BobbyDukes

    BobbyDukes Member

    Joined:
    Jan 6, 2015
    Messages:
    345
    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 :))
     
  18. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    9,985
    Gender:
    Male
    Location:
    USA / Europe
    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.
     
  19. BobbyDukes

    BobbyDukes Member

    Joined:
    Jan 6, 2015
    Messages:
    345
    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 :)
     
  20. Constatine

    Constatine Member

    Joined:
    Sep 28, 2016
    Messages:
    763
    Gender:
    Male
    Amazing substance. It would be interesting to see some experience reports. Have you personally used this substance Haidut?
     
Loading...