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LX-1031, A Tryptophan 5-hydroxylase Inhibitor That Reduces 5-HT Levels For The Potential Treatment O

Discussion in 'Scientific Studies' started by paymanz, Jun 16, 2015.

  1. paymanz

    paymanz Member

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    it is an under development drug but sounds interesting and i think it is not available on the market yet .it reduces serotonin formation in digestive system and it doesnt cross blood–brain barrier.

    http://www.ncbi.nlm.nih.gov/pubmed/21154152

    LX-1031, being developed by Lexicon Pharmaceuticals, is an oral, small-molecule tryptophan 5-hydroxylase (TPH) inhibitor that reduces 5-HT synthesis peripherally. LX-1031 is being developed for the potential treatment of diarrhea-predominant irritable bowel syndrome (IBS-D), which is characterized by excess 5-HT. In preclinical studies, LX-1031 dose-dependently reduced expression of 5-HT in the duodenum, jejunum and ileum, but had no effect on brain 5-HT levels. In ascending single-dose and multiple-dose (14 day) phase I clinical trials in healthy volunteers, LX-1031 significantly reduced urinary 5-hydroxyindoleacetic acid (5-HIAA; a marker of 5-HT metabolism) levels, starting by day 5 and persisting over the duration of exposure. In a phase II clinical trial in patients with IBS-D, a 1000-mg qid dose of LX-1031 was associated with improved weekly global scores and stool consistency, and lower urinary 5-HIAA levels over a 28-day treatment period. LX-1031 was well tolerated in trials to date. In conclusion, LX-1031 appears promising for IBS-D. Optimal doses, efficacy in IBS clinical trials and safety need to be fully elucidated.
     
  2. haidut

    haidut Member

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    Endogenous dopamine is TPH inhibitor (both TPH-1 and TPH-2), and so are dopamine agonists. As such, cabergoline, bromocriptine and lisuride have all been studies for IBS and have been found helpful in support of the serotonin theory of IBS. More importantly, you don't wait for this experimental (and probably expensive) drug to become approved as boosting dopamine or getting of the legal LSD derivatives above is much easier. It is also likely safer as these have been used for decades and their side effects are well known.
     
  3. OP
    paymanz

    paymanz Member

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    thanks for suggestion , i also think that drug gonna be expensive. have you used those drugs you suggested yourself, if yes how was them?
     
  4. haidut

    haidut Member

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    I know people who take them for years and control things like amenorrhea, diabetes and/or high prolactin. I think most people prefer bromocriptine to cabergoline as it seems to be safer. Lisuride is not available in the US, but the doctors that know about it can order it internationally.
     
  5. OP
    paymanz

    paymanz Member

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    @haidut isnt bromocriptine a serotonin agonist? dosnt that give it a negative point?
    its been said that excess serotonin cause IBS symptoms, but if i understand correct you suggested some dopamine agonist drugs, but one of them is both serotonin and dopamine agonist?
    btw i want ask your opinion about cypro for ibs treatment
    im so thankful for your replys :)
     
  6. haidut

    haidut Member

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    All ergolide drugs are mixed agonist-antagonist on the serotonin receptors, but in low doses they have predominantly dopaminergic effects. If you google around for cyproheptadine and IBS you will find info about it.
     
  7. OP
    paymanz

    paymanz Member

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    what about low does Naltrexone?
     
  8. Parsifal

    Parsifal Member

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    So LSD in high doses is serotoninergic? Hallucinations comes from serotonine?
     
  9. haidut

    haidut Member

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    I think so, it's from the agonism of one of the 5-HT2 receptors. At least that's the official theory. Also, in high doses the ergolide drugs can cause fibrosis, which is also a symptoms of serotonergic effects. Peat said LSD is an approximate antagonist to serotonin.
     
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