Anti-serotonin, Pro-dopamine Drug Approved For Psychosis And Bipolar Disease

Discussion in 'Scientific Studies' started by haidut, Mar 17, 2016.

  1. haidut

    haidut Member

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    After more than 5 decades of claiming that psychosis conditions like schizophrenia are caused by excessive dopaminergic activity and depression is a deficiency of serotonin, big pharma is doing 180 degrees reversal. A new drug was just approved for treating bipolar disorder and schizophrenia in adults, and its effects are basically a combination of cyproheptadine and bromocriptine - a combination we have discussed on the forum before. Keep in mind that current medical dogma states that the psychosis of conditions like schizophrenia is caused specifically by agonism of the D2 "receptor" and typical first-line therapy drugs for the condition are potent D2 antagonists, sometimes in combination with an SSRI.
    This newly approved drug is an agonist of the D2 and 5-HT1 "receptors" (like bromocriptine) and antagonist of the 5-HT2 and H1 "receptors" (like cyproheptadine). Sometimes I wonder how can FDA approve two drugs with clearly opposite mechanisms of action without questioning the theory behind one or the other...

    Cariprazine - Wikipedia, the free encyclopedia
    New Antipsychotic Agent Available for Bipolar Mania, Schizophrenia
    "...Vraylar is an atypical antipsychotic that exerts its effect through a combination of partial agonist activity at central dopamine D2 and serotonin 5-HT1A receptors and antagonist activity at serotonin 5-HT2A receptors. It acts as an antagonist at 5-HT2B and 5-HT2A receptors with high and moderate binding affinity as well as it binds to the histamine H1 receptors. Cariprazine shows lower binding affinity to the serotonin 5-HT2C and alpha1A- adrenergic receptors and has no appreciable affinity for cholinergic muscarinic receptors."
     
  2. Makrosky

    Makrosky Member

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    Because both of them work.
     
  3. OP
    haidut

    haidut Member

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    Then the proposed mechanism of action of one or the other is incorrect/incomplete. I am all for approving things that work but when you approve something due to the purported effectiveness of say serotonin for depression, this will taint decades of research because it will be taken more or less for granted and many more drugs will be developed based on that flawed assumption. By the same standard (i.e. "because it works") aspirin should have been approved for cancer decades ago but the official version is that until a mechanism of action is found, aspirin cannot be taken seriously as therapy, only as prevention.
     
  4. Hugh Johnson

    Hugh Johnson Member

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    But the patent has expired, so there is no political power behind it, only against it.

    Check it out. As the regulatory capture has progressed, ever more drugs are approved.
    The FDA Is Basically Approving Everything. Here's The Data To Prove It

    How does it work? One way is direct political interference:
    FDA Medical Device Approval Based on Politics, Not Science

    The other is a revolving door between the FDA and the drug companies.
    The FDA ‘Revolving Door’ Fosters Conflicts on Advisory Panels

    Basically the same as with the regulatory capture of the financial industry or 'free trade' agreements. Everything gets approved as long as there is money in it, and proof of safety and efficacy that is superficially plausible.
     
  5. OP
    haidut

    haidut Member

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    Yeah, a friend of mine works for a clinical trials company and he says that the standard of approval is basically "as long as it does not kill too many, apparently healthy, people immediately". Long term safety "studies" are actually left to the market itself. The real clinical trial is the drug being prescribed for a few decades, like Peat said.
     
  6. Parsifal

    Parsifal Member

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    @haidut I've read that Bromocriptine can be fibrotic on the long term, is that because it is an agonist of 5-HT1 receptors? So is this drug also potentially fibrotic?
    I have a schizophrenic friend who takes Abilify but I'm trying to find something better for her and not serotoninergic but this one also seems serotoninergic on this receptor and I wonder why they feel anxiety relief with agonism of this kind of reeptor as it should raise cortisol/prolactin?
     
  7. mujuro

    mujuro Member

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    This looks promising for me. I have extreme sensitivity to extrapyramidal side effects due to dopamine blockade. As little as 150mg quetiapine is enough to give me crazy twitching as I try to fall to sleep. Any other antipsychotic - asenapine, ziprasidone, lurasidone, aripiprazole - will inflict intolerable akathisia. However, aripiprazole's partial dopamine agonism makes me feel the best.
     
  8. robknob

    robknob Member

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    Any reason why this drug wouldn't work to treat heroin addicts?
     
  9. OP
    haidut

    haidut Member

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    All ergot derivatives have fibrosis as a side effect, except lisuride and metergoline. Of the dangerous ones that are in general use, I'd venture a guess that cabergoline is most dangerous as it has shown fibrosis even at the low dose of 0.25mg twice a week. Bromocriptine is probably the least dangerous as I am not aware of any published case studies of fibrosis with doses of less than 5mg. The dose approved for diabetes II is 2.5mg daily in divided doses of 0.8mg x 3. As little as 0.8mg once daily is usually enough to lower prolactin to normal range, so at the dose it should be very safe. But just to heed Peat's caution I would not use bromo for more than 3 weeks without getting some break in between.
     
  10. Parsifal

    Parsifal Member

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    Interesting. I think that I've read that the only ergot derivative that was not fibrotic is Hydergine?
     
  11. ken

    ken Member

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    I too have a friend, so I read this with interest. The view on the Internet seems to be more of the same. And it's only been available for a couple of months so the customer's haven't reviewed it yet.
     
  12. ken

    ken Member

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  13. Parsifal

    Parsifal Member

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    Good find, thanks! Don't have the time to read it as it seems really long.

    But that is possible, raising dopamine in an unhealthy body might not be that good because it becomes adrenaline soon (thus protomoting lipolysis especially with bad fat and raising nitric oxide?). This post by Dopaminergic is interesting: Psychedelics, Serotonin, And Dopamine
    It seems that even coffee can give psychosis in some context.

    On the other end I don't think that raising serotonin might be a better solution, quite the opposite.
     
  14. dilantinoid

    dilantinoid Member

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    I experienced bad akathisia on Vraylar
     
  15. aguilaroja

    aguilaroja Member

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    Hydergine (dihydroergotoxine mesylate) is a mixture of salts of 3 alkaloids (dihydroergocristine, dihydroergocornine, and dihydroergocryptine).

    Ergoloid - Wikipedia

    At least two of these salts have case reports related to fibrosis (dihydroergocristine and dihydroergocryptine):

    Dihydroergocristine-induced retroperitoneal fibrosis with an episode of reversible obstructive acute renal failure. - PubMed - NCBI
    Dihydroergocristine-induced retroperitoneal fibrosis with an episode of reversible obstructive acute renal failure.

    Pleural fibrosis associated with dihydroergocryptine treatment. - PubMed - NCBI
    Pleural fibrosis associated with dihydroergocryptine treatment.

    [Organ changes induced by ergot derivative dopamine agonist drugs: time to change treatment guidelines in Parkinson's disease?]. - PubMed - NCBI

    Medication side effects are very under-reported. When reports happen, they are inconsistent and incomplete given the large numbers probably affected. Side effect reporting tends to increase greatly when a new patented sales product is chasing market share compared to an older substance loses market. Otherwise, there is little incentive for health care businesspeople.

    Due to sparse data, it is difficult to clearly compare side effect profiles of related items. Sometimes, chemical side group and functional effects give clues.
     
  16. DaveFoster

    DaveFoster Member

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    Well there you have it then!
     
  17. bloom

    bloom Member

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    Haidut you should look at the work of Dr William Walsh. He carried on from the old-school Orthomolecular researchers Abram Hoffer, and Carl Pfeiffer. His research shows there are different 'biotypes' of schizophrenia. One group can show elevated levels of dopamine while another can show low levels. Schizophrenia, Depression ect. are most likely umbrella terms for different conditions. His research concerns the epigenetic effects various nutrients can exert. For example while everyone thinks folate increases methylation of genes, his research has found the opposite, that it predominately increases acetylation of histones. It's facinating stuff. Walsh Research Institute
     
  18. OP
    haidut

    haidut Member

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    Very interesting, thanks. Have you found parallels between his work and Peat?
     
  19. bloom

    bloom Member

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    His research is mainly focused on the epigenetic effects various nutrients have, and the effects they can have on neurotransmission. His research has found a large percentage of depressives and schizophrenics have elevated serotonin. I haven't seen many parallels between him and Peat aside from the interest in epigenetics, and the use of nutrients in a drug like way.
     
  20. passivity

    passivity Member

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    :carrot2:thumbup
     
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