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A new non-opioid pain killer (not marijuana)

Discussion in 'Science & Technology' started by ckparrothead, Aug 19, 2016.

  1. ckparrothead

    ckparrothead Draft Forum Moderator Luxury Box

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    They have custom made a new drug molecule that thus far in mice exhibits the same pain dulling capabilities of opioids without the more common side-effects (interference with breathing, constipation). And interestingly, it also bypasses the dopamine-driven addiction circuitry in the brain.

    http://www.valuewalk.com/2016/08/new-painkiller-morphine/

    Whole thing sounds fascinating as it was this big collaborative effort to go from the ground-up.

    Instead of taking morphine and tweaking its structure to try and reduce side-effects, which is the usual approach, a professor at UC San Francisco used recently discovered and known atomic structure of the mu-opioid receptor (which was discovered in 2012) to start designing brand new molecules that would bind to the receptors. Over a two week period they performed four trillion virtual experiment computations of different molecules hitting the receptor at different angles looking for candidates most likely to fit into the receptor and activate it, avoiding molecules that also stimulate beta-arrestin2 which is part of the biological pathway that leads to respiratory suppression and constipation among other side-effects.

    Once the computational squad found a number of candidates, they passed it onto a pharmacology team at UNC to make the drugs and test which are the most potent. Once that team found the most potent candidate, they enlisted the aid of a guy at Friedrich-Alexander University Erlangen-N├╝rnberg in Germany to optimize the compound's chemical efficacy.

    The result is PZM21.

    The UNC team then replicated the theoretical effects in lab mice numerous times, finding that the opioid dulled pain without respiratory suppression or constipation. In fact, they found that it would only bind to opioid circuits in the brain and would leave the spine unaffected. The opioid receptors in the spinal cord mediate pain reflexes and so affecting them wouldn't necessarily be desirable. They've not seen any opioid do this, affect the brain only and not the spine.

    They did some more behavioral tests on the mice and found that there was no drug-seeking behavior modification. Usually what happens is the mice exhibit behavior where they prefer to hang out in the chambers where they have received the opioid in the past, and this correlates with addiction behavior in humans. The mice were ambivalent toward hanging out in the drug releasing chambers. The drug also did not produce hyperactivity in the mice, which is usually triggered by activating the brain's dopamine systems.

    They'll go into human trials and that'll be the real test obviously because there are typically a lot of issues going from mice to men. But it sounds promising.
     
    CashInFist, 305, vt_dolfan and 5 others like this.
  2. Ohiophinphan

    Ohiophinphan Chaplain Staff Member Luxury Box

    I'm not sure I follow all the science. This kind of work is only now possible because of the advent of super computers and their modeling, correct?
     
  3. ckparrothead

    ckparrothead Draft Forum Moderator Luxury Box

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    Correct.
     
  4. eltos_lightfoot

    eltos_lightfoot Season Ticket Holder Club Member

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    That is crazy. Four trillion simulations. Wow. The Pharmaceutical industry is about to get real.
     
  5. Ohio Fanatic

    Ohio Fanatic 30 years and counting Club Member

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    To clarify, this technology isn't that new. while the computers are better and allow faster calculations, the end result isn't that different, just quicker.
    This is a process called virtual screening and it's something pharma has been trying for at least a couple of decades.

    The key is the crystal structure of the receptor. Receptors are MUCH harder to get real structural information (like a crystal structure) than other proteins/enzymes in the human body. Getting the real structure of the receptor allows for more accurate virtual screening.

    Overall, I agree that this is a big breakthrough. The compound still likely only has about a 5% chance of success AT BEST. probably even lower since it's targeting a receptor in the brain. But the key is that even if it fails, it can lead to better versions of this molecule down the road.
     
  6. Puka-head

    Puka-head My2nd Fav team:___vs Jets

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    No it's not. If they figure out a way to cure something they will suppress it. They make their money on symptom relief. Not cures.
     
  7. RevRick

    RevRick Long Haired Leaping Gnome Club Member

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    Well, I am trying something called Belbuca for relief of fibro pain. There are days I wake up at straight level 8 pain - and then it gets worse. Most days, I run at level 4-5. The opiods would work, but after about 50 mg. the fog from the medicine was worse than the fibrofog. It was getting hard to work through the fibro pain on the point of passing out. I would walk each day trying to find the balance which would hold off the pain and yet not debilitate me. The Belbuca takes most of the pain most days - which is a great net win. It will not stop all of the pain any day, but most and most are far better than I have had for six years.
     
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  8. Puka-head

    Puka-head My2nd Fav team:___vs Jets

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    I'm going to look at that.

    My Mom is a Doctor of Nursing, published PhD and she is telling me about low dose meltroxelone. Not common amongst the pharma factories but Naturo-paths and others are finding it effective.

    I gave up on opioids after taking 80mg of hydro AND 80 mg of Oxi a day for years. Looked at baby girl looking at me and wondering where I was and decided that was enough of that one day. . The cure was worse than the disease. I replaced that with Marijuana and feel a billion times better. Edibles are most effective but smoking is fastest. I'm encouraged by the new research into CBD's that are not as psychoactive, but I don't hate the buzz anyway so...;)

    I also learned a lot about mind control and how the brain uses pain to distract from stress, anxiety and depression. A book called the "Mind Body Connection" By Dr James Sarno was the start of that journey. The brain exploits the weak points or injuries and sends pain signals to itself to distract from the emotional stress and force you to focus on the pain. I have found that when I can convince myself that even though it hurts more today, it's not because I am more injured than I was yesterday, and why I hurt more is because I don't want to deal with stress # 74 today I am able to function at a much higher level.

    And some days I just...can't.

    But you just keep swimming Rev, just keep swimming.
     
  9. RevRick

    RevRick Long Haired Leaping Gnome Club Member

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    Yeah. I know what you mean. I was on an average of 150 mg/day. My wife said it made me more foggy than the fibro any day. To make matter even more interesting, and I have had two doctors disagree with the diagnosis, and two concur with it so fibro is still in the neverneverland of medical practice and no one has any pixie dust to make the pain disappear. If it works, it either knocks one on their tukkis or it is illegal. I haven't smoked (either tobacco or ganja) for 35 years now and as a pastor, smoking rope would be a little outside the boundary - even if I had a prescription - which is NOT going to happen up here!

    And then there are the 'nimnodes' (from an oulde Star Trek episode, BTW) who are convinced that there is no such thing as fibro. I would love for the BOSS to allow some of them to experience a full flare for 24 hours and send Gabriel (in full celestial garb) to let them know that is how some people live 24/365!

    I know just what you mean about "Some Days!" It is only because of the power of God that "some days" I am able to do what is necessary. My faith has allowed me to do what on "some days" that would normally keep me flat on my back. But, the price for being a conduit of that kind of power is that you feel like you would lose an arm wrestling match with a kitten for most of the rest of that day, or for me for all of Monday. (I have two services and a Sunday School class most Sundays.) That is as close to "mind control" as I have come. I am reminded of what to an old Navy buddy would say as of one of our old sayings from 'back in the day' - or in other words 45 or so years ago! Mind over matter.. If you don't mind, it don't matter.) Works once in a while. But then.......

    Y'know... Living with constant pain at any level is at best difficult, and some days, to quote another one of our old Navy sayings "f****** near impossible." So just remember the old Navy Seabees motto - "The difficult we do quickly. The impossible takes a little longer."

    The Lord be with you!
     

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