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Metergoline - Serotonin Antagonist & Dopamine Agonist For R&D

  1. 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. 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. 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. 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. 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. 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. 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. 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.
     
  9. Holy smokes! Order shipped! Let me just bow down a few times on my Washington-directed carpet.
     
  10. Lol, thanks. I can settle for the title "rogue nutritionist". Sort of like gastronomical "haidut" :)
     
  11. I fail to see how this differs from lisuride or even ritanserin
     
  12. 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. 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. 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. Interesting; thanks for clarifying.

    This made me think otherwise; there's a typo by the way, just noticed.
     
  16. Fixed the typos, thanks for noticing them.
     
  17. 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. 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. 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. Amazing substance. It would be interesting to see some experience reports. Have you personally used this substance Haidut?
     
  21. Yep, I like it the most from all serotonin antagonists I have tried. When used on its own it is better than ritanserin and in combination with lisuride is a great anti-stress and pro-metabolic tool. Also, for me it is really good a alleviating IBS symptoms when I eat very spicy food or a lot of starch.
     
  22. This seems pretty similar to quinine. Have you done much experimenting with Quinine, does it feel similar?
     
  23. Hmm; I'm interested in making a purchase.

    Why do you use it in combination with lisuride? Is there not sufficient overlap that a higher dose of metergoline could not achieve on its own?

    Also, do you know metergoline's effect with regard to blood pressure? I'd assume lower doses decrease blood pressure, while higher doses would result in an increase.

    Lastly, have you used metergoline/lisuride with caffeine, and do you find they have additive effects or rather mostly overlap in their effects? I guess what I'm asking is: do you think that the ergot derivatives/dopamine agonists possess positive effects beyond those of caffeine alone?
     
  24. I don't always use it with lisuride. When I do use it with lisuride it is because of the synergistic effects as described in the original post. For drugs like bromocriptine, metergoline blocks their potential fibrotic side effects.
     
  25. Why is it similar to quinine? I don't see any similarity in structure...
     
  26. Structure would be different. I could have sworn that I read Metergoline was a TPH inhibitor...but I can't find where I read that now.
     
  27. Thanks for elaborating.

    About the blood pressure; the reason I asked was this:

    Cardiovascular effects of lisuride continuous intravenous infusion in fluctuating Parkinson's disease. - PubMed - NCBI

    "The cardiovascular effects of a continuous intravenous infusion of lisuride plus oral domperidone were studied in 16 fluctuating parkinsonian patients as compared to their usual oral therapy with levodopa plus carbidopa. The study was performed using a 24-h ambulatory recording and an automatic noninvasive device for blood pressure monitoring. During lisuride infusion, a significant increase of systolic blood pressure was observed; however, in three patients, a decrease of systolic-diastolic blood pressure occurred; furthermore, a mild increase of atrial arrhythmias and, in two patients, a short run of atrial fibrillation were noted. Asymptomatic orthostatic hypotension, observed in seven patients during levodopa therapy, disappeared during lisuride infusion. Paradoxical hypertensive effects and disappearance of orthostatic hypotension observed in our patients seem related to the concurrent administration of domperidone."

    On second look, I realize that they credit it to domperidone, the D2 antagonist used in this study, which would raise serotonin, so pay me no mind.
     
  28. Longtime lurker here, this thread got me to register. Depending on how reviews go I might order this in the future :)
     
  29. Dopamine and dopamine agonists are TPH inhibitors. So, if metergoline is indeed a D2 agonist then it should reduce serotonin synthesis. In fact, one of the studies posted in the references section says metergoline lowers serotonin synthesis, so maybe that's the one you are remembering.
     
  30. Haidut what payment options does your website have?
     
  31. Well, credit cards would be the only real option right now. We used to have PayPal, which allowed us to get echeck and money transfers but we don't have PayPal any more.
     
  32. Metergoline is a 5HT3 and 5HT4 antagonist which helps with IBS-C and IBS-D ?
     
  33. Would there be any problems taking metergoline and acetazolamide at the same time?
     
  34. I don't know that it is a 5-HT3 antagonist. It is considered non-specific serotonin antagonist, which means that in sufficiently high doses it should antagonize ALL serotonin "receptors". But in the realistic doses of 2mg - 4mg daily it is certainly a 5-HT1, 5-HT2, 5-HT6 and 5-HT7 antagonist and that alone has some very beneficial effects on IBS. The 5-HT3 antagonists are useful mostly for diarrhea and nausea, not so much IBS.
     
  35. Could this be useful for autism? Any research/thoughts?
     
  36. Here's the fully-titlified references, I think the forum gave up partway through:

    Miscellaneous

    Neurological/Brain

    Mood/Cognition/Behavior/Addiction

    CVD/Circulation/Hypertension/Calcification

    Fibrosis/Cancer

    Metabolism/Diabetes/Cortisol/Insulin/Obesity

    Digestion/GI

    Immune/Antirival/Antibacterial/Antiparasitic
     
  37. Considering serotonin's apparent role in autism I would assume metergoline would help. Bottom line it doesn't seem dangerous so its worth a try.
     
  38. I would think so. However, autism, I think, is more than a serotonin issue. Just take a look at @scarlettsmum's posts; she made observable progress with other serotonin antagonists. However, inflexibility and rigidity remain as big issues. This is the case in my own experience with my sons, too. I don't know what it is causing that but it suggests to me that there are other things in play as well.

    @5magicbeans
     
  39. Serotonin and opioid excess is linked to many forms of autism, including austim spectrum disorders and aspergers syndrome there is no doubt about that.
     
  40. Anything that blocks the 5-HT2 receptor is potentially useful. Search the forum for cyproheptadine autism.
     
  41. Not happy with the sleepy side affect of cypro....what about metergoline?
     
  42. I don't find it sedating but that's just me. The sedation from cypro is mostly from the antihistamine action.
     
  43. Do you think this could potentially regrow a rat's hair? The prostaglandin antagonist interests me.

    Also, is this substance better taken at night or the morning?
     
  44. I am not aware of any studies with it for hair growth. It can be taken any time of the day but in higher doses its dopaminergic agonism probably becomes stronger so if taking more than 4mg in a single dose I would take in the morning as is the recommendation for other dopamine agonists.
     
  45. Thanks
     
  46. Is this thought to be more or less dopaminergic and more or less anti-prolactin than lisuride? If one has a stockpile of cyproheptadine and using it with lisuride I wonder if there would be anything metergoline would do making it worth any extra investment...
     
  47. For maximum effect it should be combined with a dopamine agonist like bromocriptine or lisuride. But for people who only want to experiment with 1 chemical on their rats, metergoline would be the way to go I think. Of course it also depends on what chemical the rat can handle the best with the least side effects. Rats are different and just because one chemical sounds great on paper does not mean that it will pan out like that in the real world.
    Btw, this very issue is discussed in the original post.
     
  48. Is there any chance these substances are being tested for whats inside?
    Personally id like to know.
     
  49. We just contracted a lab in North Carolina that will do the testing. The testing will start in first week of November, so I am hoping that by the end of the year we will actually have a COA for every single supplement.
     
  50. That sounds awesome
     
  51. hi new member here,

    two questions,

    does metergoline have antihistamine action?
    is it anticholinergic?
     
  52. It does seem to have some of both activity but it is rather weak to be of clinical significance.
    Effect of two antiserotoninergic drugs, methysergide and metergoline, on gastric acid secretion and gastrin release in healthy man
    "...The effects of acute oral administration of the antiserotoninergic drugs methysergide (3 mg) and metergoline (4 mg) on basal, submaximal (0.6 µg/kg i. m.) and maximal (6 µg/kg) pentagastrinstimulated gastric acid secretion, as well as on basal and food-induced gastrin release, have been evaluated in healthy volunteers. Methysergide significantly increased basal and submaximal pentagastrin-stimulated gastric acid secretion, and metergoline significantly inhibited gastric acidity in all experiments. Basal and stimulated serum gastrin concentrations were not modified by either drug. The effect of methysergide on gastric acid secretion was opposed to that of serotonin and was probably dependent on its antiserotoninergic action, but the decrease in gastric acidity caused by metergoline is not easily explained. Although the effect is similar to that of a dopamine infusion, it does not depend on dopamine receptor stimulation, since it was not influenced by pretreatment with metoclopramide. It is suggested that it might be due to the weak anticholinergic and/or antihistaminic properties of metergoline."
     
  53. I'm assuming due to the prolactin lowering effect it could def boost libido and T/DHT?
     
  54. Hi Haidut,
    Do you have any comment on how you think this his would compare with other anti-serotonin agents for treating migraine? Prophylactically or abortive? Likely withdrawal effects?
     
  55. Hi tara,
    I definitely don't want to jump over Haidut's answer to you.
    But as an aside, if the question was for yourself, have you tried buteyko breathing?
    I tried the Control Pause test tonight and did terrible. Like 20 seconds.
    And really, we do a lot of breathing exercises in my training and I still sucked at Buteyko.
    We do something similar in my school called Misogi breathing. Whenever we do it, I just cheat. Absurd, I know.

    Though they never tell us why we do the things we do in training (they believe in physical transmission- not scripture or lecture), it is very interesting that they came up with the same goal as Buteyko. The main teacher who does Misogi can do the exhale for 3 minutes. It's just weird.

    But now there are enough data points that this is something to pursue.
     
  56. It has been used for migraines and it is approved as migraine drug in some countries. I don't know if it treats it, as migraines are a metabolic disease. Broda Barnes has a few quotes on this forum saying once thyroid function improves the migraines disappear and do not return unless hypothyroidism sets in again. But anti-serotonin chemicals definitely have their place for daily treatment while working on thyroid and diet.
     
  57. Im not sure exactly how serotonin affects the thyroid, but im 100% sure that TSH and prolactin are linked (think of subclinical hypothyroidism)
    And chances are high Ive seen this many times, including myself years ago when I was in a state of constant stress bombardement.
    Having used 50-75mcg levothyroxine in the morning on empty stomach got my prolactin levels down from top end of the range to low-middle ish range.
     
  58. Hey Haidut,
    My rat does not respond to Ritanserin, Lisuride or Androsterone.
    My rat is very depressed and Tianeptine Sulfate provides substantial relief only when taken every 3 or 4 days.
    My rat also does well with Methylphenidate but tolerance seems to build rapidly, and so again, cycling is necessary.
    Based on the foregoing, is there reason to believe Metergoline could provide benefit?
    Rat is desperate, recovering from Klonopin withdrawal syndrome, has bipolar depression, and the mornings are gratuitously difficult.
     
  59. Thanks Haidut.
     
  60. :hearteyes:
     
  61. Yeah, the testing is really cool, thanks for going above-and-beyond, Haidut.
     
  62. My rat just started using this. What effects should be apparent with moderate use?
     
  63. First night subject tried 4 drops. Mild nausea, things felt really good, very frequent arousal, mental clarity. The next day, subject tried 1 drop and noticed some lowered self esteem and unwillingness to socialize. This continued with future doses of 2 drops. Sleep has been good.
     
  64. I have also felt a slight increase in anxiety and perhaps lowered self esteem on 8 drops. There do seem to be some positive effects but I wonder if this anxiety stems from a lack of inhibitory neurotransmitters. This is may be very oversimplified thinking but I suppose an increase in gaba is warranted to counteract the negative effects.
     
  65. Please keep us updated on how you feel on using this
     
  66. @haidut

    How does Metergoline differ from the more readily available Nicergoline (which is apparently a standard pharmacy item in many countries)
     
  67. Research subject started with 4 drops of Metergoline. Within 15 minutes subject body felt warmer and a little restless.
    Subject needed a change of environment, as subject suffers from high stress/depression.
    Metabolism seemed to increase and subject was given 3 coca cola's 355ml to bring for the walk. Outside subjects mood increased some.
    15 minutes later on walk subject received 4 more drops. Subject noticed first person they saw looked like Ray Peat. Subject felt it was an interesting coincidence.
    Subject noticed some anti-depressant/anti-stress effects. Subject mentioned that Metergoline was better any SSRI/SNRI they have tried. From first time use effects, to overall effect as some medications are said to require time to build up.

    Subject started to sing while walking. 30 minutes later subject took another 4 drops. Then another 4 drops 30 minutes later(16 drops total).
    Subject did not feel the effects(anti stress/depression) increase or decrease anymore than the first 8 drops. Subject reported their energy was stable while walking around 9000 steps total for the walk which they recorded.
    Subject only stopped 1x for a few minutes. Sang around 5 songs total. Sweated a lot due to wearing many layers of clothing to keep warm. All 3 coke's were drank during the walk, and took 3 pee breaks.

    As subject was walking back to their cage while listening to Ray Peat talking on KMUD about authoritarianism they noticed a football game going being played. They felt sad for the people.
    Possible head/body injuries. When they could be connecting on different levels through chemical/technology/science types of means. Subject did mention they have experienced concussions and a few knockouts in their lifetime.

    Subject seemed a little more tired than usual when subject was back to it's cage. Could have been due to needing more food. Subject ate and felt better. Metabolism was high throughout the evening.
    Subject mentioned that they did not notice much of an increase in warmer/loving type feeling as they have had on other medications. Though was still ready to engage people for a positive or negative situation.
    As in making new friends or defending themselves. Sociability stayed the same.

    They did not have a overwhelming sense of pleasure or depression. Felt pretty balanced. Less stress/depression.
    Subject has a hard time describing things.

    3 hours from first drop subject took another 8 drops(24 drops of Metergoline total). Felt no different from the first 8 drops.
    Subject felt it was a safe substance. Felt it was interesting that the effect did not intensify past the first 8 drops.
    Subject listened to some new music music they downloaded months ago but never bothered to listen to yet.

    1 hour later subject took 8 drops of Lisuride. Did say they noticed a calmer type thinking as subject has complained in the past about there thinking being too spread out with different thoughts(probably from stress/depression).
    Subject felt less thoughts in their mind.
    1 hour later subject took another 8 drops of Lisuride(16 total). Took 20 minutes of full body red light. Did not notice much of a change positive or negative from first Lisuride dose. Perhaps more calm?

    Subject's libido did not increase or decrease to any significant degree during the whole duration.
    Subject had no problem falling asleep before 11pm.

    Subject's sleeping did appear to improve slightly, as in less times restless and awoke with a clearer head/less stress. Total sleep time did not improve.
    Slight anti-depressant/less stress effects are still noticed 10 hours after last dose taken.

    Subject took 4 drops of Metergoline and Lisuride this morning. Noticed metabolism increase and same feeling as yesterday's.
     
  68. Time of the day was it taken? And also, seems a bit much to use?? Why not stick to the 4-8 drop dose for a few days and report back?
    Either way thanks for the report :)
     
  69. Oh I see, I wonder if there would be any tollerance building up eventually.
    Also wouldnt it be wiser to take it first thing in the morning as the half life seems to be 12hours as pointed out by Haidut.
     
  70. Metergoline seems to make my subject much more motivated. Subject tends to feel much more responsible and productive on the substance. Mood is stable. Will keep updating.
     
  71. I agree with Quality.

    I think the opioid system is underplayed as a factor in depression, autism, and autoimmunity.

    Peat has said that using a selective opioid antagonist, such as naltrexone possess powerful downstream affects that disrupt the influences of estrogen and histamine on the cell.
     
  72. I've tried most of these now - this one (so far only a couple times), the lisuride, the ritanserin - and I can't feel anything from any of them at ALL.

    Granted, this is normal for me with most substances, but with these tiny bottles I'm feeling extra frustrated. I've irrationally and rudely thought perhaps they were blanks - just DMSO and nothing else. But the fact that others do have reaction assure me I'm being silly.

    Still - what's wrong with me that I have no reaction? Is there a compound that can 'potentiate' these? I've taken slightly higher doses, or mixed them together, with no effect.

    What am I missing??

    This non-reaction has been the norm for years. Most of that time I've been pretty healthy, but the past few months dealing with pretty horrible insomnia. But I doubt that whatever is causing the insomnia is related to my non-response.

    I'm just venting here, apologies for any rant. I think Haidut's products are amazing - I just wish I could FEEL them.
     
  73. You are not alone. My rat has yet to try metergoline, but I am hesistant to waste extra cash on it, knowing that I have not had any favorable reaction to both lisuride and ritanserin. plus I don't want to go down that rabbit hole of increasing the dose just to feel something from it not knowing what the negative consequences are with higher dosing of these chemicals.

    For some reason, I get a more favorable reaction to just taking lysine. I'd like to know what's up with that, and why my rat is not a good responder to the above mentioned chemicals.
     
  74. Research Subject finished it's 2 day (weekend) experiment with metergoline/lisuride.
    That is why subject got a higher dose first use. Subject noticed a build up effect as it might be from the half life times.
    Subject did 4 drops of each 2x on Saturday morning/evening. Then did 2 drops of each 1x on Sunday.
    Subject feels it cannot give a definitive response to their experience to others due to short time usage. Interesting to say the least on the experiment.
    Not everyone should expect same experience that this research subject had. As a few people mentioned above there research subjects not getting much of a reaction from some of these substances. Which is unfortunate.

    Subject feels this substance could be judged better doing a longer term experiment using low dose. Bridging up dose if needed.

    Perhaps dosages around 1-4 drops of each(or even just 1 ergoline) 2x a day would be enough for other subjects depending on what they use it for. Might help adhd/add, or daytime fatigue with a stimulation effect.
    Subject did get some anxiety at times wanting to change some stressors in their environment/life.
    Seemed more motivated overall, some day time fatigue issues prior to use were felt less with these 2 substances.

    Subject is impatient and never intended to use it for a long time. Subject is doing alright with the basic stuff like vitamins/minerals/hormones/herbs/aspirin etc.

    Subject was researched on using these ergolines to try this to compare different substances used around the world for certain conditions like anxiety/depression/Parkinson's/migraines so they could get a better understanding on what is being used, and have an experience.

    Thanks to Haidut for making these things available for research.
     
  75. Nicergoline has none of the anti-serotonin and pro-dopamine effects of metergoline. In fact, other than the similar structure I am not sure they have anything in common functionally.
     
  76. The rat could try some metergoline but of course there are no guaranteed. Methylene blue seems to work really well for both unipolar and bipolar depression. There are human studies showing complete reversal with 15mg daily for just 2 weeks.
     
  77. My Little Hamster is a typ 1 Diabetic and i have read through the research that was posted on Meterg. It always says "Chemical induced Diabetes"...so is this equivalent to Typ 1 Diabetes?

    On a side note

    Hamsters Bloodsugars have been surprisingly good with the use of Androsterone 2x 3 drops a day
     
  78. The chemical induced diabetes is a condition that mimics human type I diabetes - i.e. the scientists destroy the animals' pancreas with some toxic chemical and the animal cannot produce insulin any more. So, it should be a pretty good model of human diabetes.
    The androsterone effect on blood sugar is not surprising. Ray said that all strong androgens improve oxidation of glucose and lower cortisol (which improves insulin sensitivity). So, if you are having good results with androsterone than maybe no need to mess with metergoline unless you are into rat experiments with cool chemicals :)
     
  79. Oh wow thanks Haidut for explaining this.
    Yeah me and my Hamster are totally into cool Chemicals☺
     
  80. Updates? Have you conquered the business world yet like haidut?
     
  81. I would not waste money on metergoline if you did not react to lisuride which is a stronger substance in my opinion. Also what are you hoping to accomplish with serotonin antagonists? If your mood is already stable then I doubt metergoline would be of much use to you. It seems to me metergoline just makes my rat feel normal hence if you are already in a good place I doubt it would help.
     
  82. No but I have conquered the computer science world. Writing code is noticeably easier on metergoline unless I take too much. If I take 8 drops I feel pretty zoned. Its not difficult to think in such a state and its very relaxing but its not productive for work. A good dose is 2 - 4 drops. On this dose my head is very clear and I am very motivated. However the motivation does not seem to stem from any dopamine related pathways (if I may say so anecdotally) but rather it stems from increased awareness of my surroundings. I think peat said that serotonin acts as a mask to the senses, with this mask lifted all you responsibilities become clear.
     
  83. Interesting; thanks for the reply.
     
  84. Yet Nicergoline is still prescribed for cognitive dysfunction, unsteadiness, dementia and other issues in several countries. So possibly it has benefits besides the anti-serotonin and pro-dopamine effects?
     
  85. Quick update: Metergoline seems to dramatically lower inhibition but it lacks the other effects of alcohol thus it is not really noticeable. You tend to realize you were very social and outgoing after events. I remember reading that serotonin is inversely related to risk taking behavior and this is apparent on Metergoline. My rat says it seems to root him in the moment which is pretty nice. Makes a very good pro social and even pro general experience substance, though it does decrease behavioral inhibition a lot so be careful you don't start fights or tell your wife her cooking sucks...
    Also it makes my rat want to go out and have fun versus do work... which requires some self discipline.

    Here is an interesting study regarding serotonin's role in behavioral inhibition: Reconciling the Role of Serotonin in Behavioral Inhibition and Aversion: Acute Tryptophan Depletion Abolishes Punishment-Induced Inhibition in Humans | Journal of Neuroscience
     
  86. That's awesome. You had used lisuride before? Did you find that or other serotonin antagonists to feel comparable in terms of the drop in social inhibition?
     
  87. I have not used lisuride before. Metergoline is my rat's first strong serotonin antagonist but I am sure lisuride will have a similar effect (the effect might even be greater due to more pronounced dopamine agonism). I am planning for my rat to experiment with lisuride by itself and in combo with metergoline and will keep this thread updated. Also just to clarify the reduced social inhibition does not stem from reduced anxiety but from something else entirely. You kind of just find yourself doing things naturally...very strange.
     
  88. Hi Constatine,
    First of all would like to thank you for the experience updates you have done and please continue to keep doing so.
    I will give this a try next month when my money arrives, is there any chance the other people who ordered this can also give some updates about it.

    ps. what dose were you using Constatine?
     
  89. That's great feedback! Any info on dosage for the rat?
     
  90. My rat is using 2 drops on weekdays and 5 drops on weekends for an added pro social effect. The difference in effect between dosages is only barely noticeable though, but it is there.
     
  91. Thats good to know.
    Im curious how long term chronic treatment would work out, regarding tollerance and possible side effects as such.
     
  92. How many drops are there in total in the container?
     
  93. Seriously, this information is in this very thread. Did you read the original post?
     
  94. I kinda got lost in the thread couldnt remember if it was in the first post but it is.
     
  95. I'll report any side effects as time goes on. The only side effect my rat has experienced so far is an increase in anxiety...however it is a very strange occurance. This anxiety actually feels good and refreshing for some reason and is more akin to excitement I think.

    Experience report: I have noticed that my rat feels much like a little kid on metergoline (not a decrease in manly personality traits but rather an increase in playful behavior). My rat feels like he wants to go snowboarding, partying, and hiking on metergoline. I will try to observe any negative side effects as time goes on and will keep you all in the loop. Also I encourage anyone else taking this to share your experience reports as everyone is different.
     
  96. Agree there with the anxiety thing constatine, some mild anxiety is always good imo, makes you appreciate the smaller things in life more.
    Has to do with nociception I personally think, pain and pleasure are closely intertwined in the brain.
     
  97. Dosed 4 drops this afternoon. It is super energising. 12 hours later I can't sleep but I feel great - I've been dancing naked in my room for hours! I didn't have such a good response with Ritanserin and the Lisuride was probably too dopaminergic for me. This is the sweet spot! Wondering if I can combine it with cypro/ if that's really necessary/but possibly need something sedating for evenings.
     
  98. I would really like to know if there's a rat that absolutely couldn't tolerate lisuride that did well on metergoline? And possibly how they'd compare to bromocriptine.
     
  99. I feel the same way - metergoline may well be the sweet spot for a single anti-serotonin chemical to experiment with and without the need for additional dopaminergic chemical. I don't think cypro will add much except the anti-cholinergic and stronger antihistamine effects, which may or may not be needed depending on the situation.