Idealabs Comments And Suggestions

Discussion in 'IdeaLabs' started by Ras, Feb 25, 2016.

  1. johnwester130

    johnwester130 Member

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  2. haidut

    haidut Member

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    These studies below show metergoline antagonized the effects of 5-HT1A agonists, which is a common criteria for something being an antagonist at that receptor.
    Pharmacology of the hypothermic response to 5-HT1A receptor activation in humans. - PubMed - NCBI
    Are 5-HT1A autoreceptors involved in the inhibitory effect of ipsapirone on cold-elicited thyrotropin secretion? - PubMed - NCBI
    Effect of metergoline, fenfluramine, and 8-OHDPAT on catalepsy induced by haloperidol or morphine. - PubMed - NCBI
     
  3. Brooks Esq.

    Brooks Esq. Member

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    Yes I'm still sure. WAY 100635 and Lecozotan are the only potent; selective 5ht1a antagonists. The other ones on that page are weak ligands or do not work with the potency needed to reverse this condition. Some of them are only antagonists on autoreceptors.
     
  4. Brooks Esq.

    Brooks Esq. Member

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    I reviewed these studies you provided. If you read these cases closely you will see that Metergoline helped eliminate some of the effects brought on by 5ht1a agonists, but this does not indicate that Metergoline is a 5ht1a antagonist. For instance, if I take an antidepressant and suffer a headache, I then take an aspirin which helps ease my headache, it does not mean that the aspirin was an antagonist to the antidepressants mechanism of action, nor does it mean I had an aspirin deficiency which caused the headache.

    Please take a look at this full biological activity page that maps out all of Metergoline's pharmacology, please see that 5ht1a is not affected by metergoline.
    metergoline | Ligand page | IUPHAR/BPS Guide to PHARMACOLOGY
     
  5. sladerunner69

    sladerunner69 Member

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    My chief concern with administering 5-ar would be suppression... Would really by a trainwreck if my 5-ar became supressed again or if it has some kind of detrimental effect on the nervous system. Some people think the problem lies within the nervous system and not necessarily with low 5-ar. Has anyone here had 5-ar levels tested? @TubZy
     
  6. sladerunner69

    sladerunner69 Member

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  7. TubZy

    TubZy Member

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    I had not had 5AR tested but I have normal DHT and testosterone levels along with many others. So the 5AR has to be working somewhat at least.

    My theory is that increasing 5AR will help create a positive feedback loop for all of the other missing pathways besides DHT associated with it which really seems to be where the issues is IMO.
     
  8. haidut

    haidut Member

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    See links below. The second link shows that metergoline is not much weaker than the known 5-HT1A antagonist NAN-190 (NAN-190 - Wikipedia) and has Ki value of just 1.2nM for 5-HT1A, making it a quite potent 5-HT1A antagonist and more potent than the other known 5-HT1A antagonists spiperone and methiothepin.
    Serotonin: Molecular Biology, Receptors and Functional Effects
    "...On the other hand, the sumatriptan-induced contraction of the dog saphenous vein (Humphrey et al. 1988) and the indorenate-induced reduction in the porcine carotid arteriovenous anastomotic blood flow (Villalon et al. 1990) are both resistant to metergoline which has high affinity for 5-HT1A, 5-HT1B, 5-HT1C and 5-HT1D receptors (Hoyer 1989)."

    http://www.perkinelmer.com/Content/TDLotSheet/6110501400UA_423-551-A.pdf
     

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  9. Drareg

    Drareg Member

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    I can't find much more on these substances,do you have any experience with them?

    DHT Butyrate -https://en.m.wikipedia.org/wiki/Dihydrotestosterone_butyrate
    DHT acetate -https://en.m.wikipedia.org/wiki/Dihydrotestosterone_acetate
     
  10. haidut

    haidut Member

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    These are just esters of DHT, so not much different than the steroid itself. Still considered controlled substances in the USA and most other countries.
     
  11. Drareg

    Drareg Member

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    Thanks.

    In relation to the substances that potently lower cortisol like metergoline and androsterone,they are potent dissolved in DMSO as you mentioned before. Do you think people are possibly pushing cortisol a touch lower than normal and experiencing the effects they are mentioning with said substances?
     
  12. haidut

    haidut Member

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    That I don't know. Only blood tests would show for sure but morning fatigue is sometimes a symptom of low cortisol so it is certainly possible. Getting joint pain is also a possible symptom of low cortisol / estrogen.
     
  13. Drareg

    Drareg Member

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    I was guessing if the substances we use on here that can cause a touch of water retention at times is because of them taking cortisol a touch lower. I will look into it more, labs are absolutely necessary,nevertheless we can speculate.
    Mertogoline works for cushings as does cyproheptadine.
     
  14. haidut

    haidut Member

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    Yep, the anti-cortisol of metergoline is given. Most anti-serotonin drugs and some of the dopamine agonists like lisuride and bromocriptine, can be used for Cushing syndrome. There are quite a few studies on that. I suspect metergoline may be a bit more effective than cypro for cortisol as it had potent antidepressant effect even as a single dose weekly.
     
  15. Drareg

    Drareg Member

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    Your supplements are serious quality,the only side effect is doing too much of them.
    The authority will be all over you if cushings patients latch on to them,they could have reversal of symptoms within hours.
     
  16. haidut

    haidut Member

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    Well, our cyproheptadine is for R&D use only. How it is being used is up to the people buying it. It is not much different from ketotifen, which is also available in liquid form as a R&D chemical from US vendors.
     
  17. Brooks Esq.

    Brooks Esq. Member

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    Thank you for sending this, but I don't know that this helps your claim of metergoline being a potent 5ht1a antagonist. This study actually is about a test subject being given a 5ht1a agonist, and metergoline was not strong enough to override its agonist affect at the 5ht1a receptor. The study was very old and the scientists were working on the theory that Metergoline was a 5ht1 antagonist as a whole (which more recent pubmed studies have proven to be methodologically wrong).
    Assuming that Metergoline was a 5ht1a antagonist, it would be too weak to have any real effect at the post synaptic receptor.

    Mr.Haidut, I have enjoyed the exchange of information, but I did not post my question because I wanted to engage in a informational debate about metergolines effects. Metergoline is a good product and has been able to reverse some of the endocrinologic damage brought by ssri, but it does not treat PSSD!

    I would still like to ask if your company would be open to any production proposals of Lecozotan, if someone would help front production costs, or if there is any scenario where idealabs would consider producing Lecozotan as a one-time test run to see how it sells. If it works it would be extremely profitable to Idealabs and we would finally know if a potent antagonist of 5ht1a is the cure to PSSD.

    Please at least consider it, I would appreciate it and so would many others, please find it in your heart to at least weigh the idea.

    Brooks
     
  18. haidut

    haidut Member

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    OK, I will look into it.
     
  19. Agent207

    Agent207 Member

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  20. Pointless

    Pointless Member

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    Glutamatergic and cholinergic makes it sound like it would be excitotoxic for the parasympathetic nervous system.
     
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