Researchers Create “Unprecedented, Weird and Cool” Opioid Painkiller from Scratch

Researchers Create “Unprecedented, Weird and Cool” Opioid Painkiller from Scratch

By Staff

Researchers from U.C. San Francisco, Stanford University, the University of North Carolina and the Friedrich-Alexander University Erlangen-Nürnberg have cooked up a new opioid drug candidate from scratch that they say can block pain without triggering the dangerous side effects of painkillers.

Their study was published this week in Nature showing the computational techniques that allowed them to explore more than four trillion different chemical interactions.  They used a newly deciphered atomic structure of the brain’s “morphine receptor” to cook up a novel drug candidate from scratch, and it blocked pain as effectively as morphine in experiments using mice.  The notable outcome was that the new drug did not share the “potentially deadly side effects typical of opioid drugs,” such as depressed breathing, constipation or drug-seeking behavior in the mice.

“Morphine transformed medicine,” said Brian Shoichet, PhD, a professor of pharmaceutical chemistry in UC San Francisco’s School of Pharmacy and co-senior author on the new paper.  “There are so many medical procedures we can do now because we know we can control the pain afterwards.  But it’s obviously dangerous too.  People have been searching for a safer replacement for standard opioids for decades.”

Shoichet says that, much of the drug discovery begins by taking a successful drug like morphine and tweaking its structure to try to get rid of side effects.  The new study took a different, much more radical approach: “We didn’t want to just optimize chemistry that already existed,” Shoichet said.  “We wanted to get new chemistry that would confer completely new biology.”

“With traditional forms of drug discovery, you’re locked into a little chemical box,” Shoichet said.  “But when you start with the structure of the receptor you want to target, you can throw all those constraints away.  You’re empowered to imagine all sorts of things that you couldn’t even think about before.”

Through their extreme computational approach, called molecular docking, they performed four trillion “virtual experiments” simulating how millions of drug candidates could morph and twist, and looked for the results that were most likely to fit into a pocket in the receptor and activate it.  They found a short list of 23 potential candidate molecules, and ultimately created a molecule that they called PZM21, which is chemically unrelated to existing opioid drugs.

PZM21 appeared to dull pain by affecting opioid circuits in the brain only, with little effect the on opioid receptors in the spinal cord that mediate pain reflexes.  No other opioid has such a specific effect, Shoichet said, calling it “unprecedented, weird and cool.”

Image courtesy of www.ucsf.edu

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Authored by: Staff

There are 23 comments for this article
  1. Judy Jaeger at 6:02 pm

    Sorry but I don’t trust Big Pharma enough to be willing to be a guinea pig for any new drug.
    They don’t have a good track record. Just about every prescription I’ve ever been on has turned into a nightmare, causing all kinds of problems that lead to more health issues. So, I’ll take a pass.

  2. Barbara at 1:35 am

    I hate to just repeat what so many have already stated but I too would be interested in clinical trials if this product makes it to that point. Although calling the results “weird and cool” gives me pause. It is not exactly research terminology.

  3. connie at 4:37 am

    In most drug trials, especially for pain meds, you have to be completely off all pain meds for a period of time before they will accept you to participate. At least that is what I was told years ago when I tried to get in a drug trial.

  4. Cliff at 9:31 am

    FLIYING CARS?? How about when PIGS FLY?? Don’t forget about the other drug companies interest in this. If anything, I think it would be bought and shelved . Also the government would hate to see their HOLD on millions of be taken away….The CDC ( government ) morons do not see chronic pain patients like us, only drug seekers…. We are not being believed anymore.

  5. Jessamyn Butler at 8:37 am

    I would GLADLY sign up for the first (and successive) human trials. I am way too young to be confined to my pain. Check the CDC trials in the future–I have it bookmarked on my computer, and check often!

  6. HJ at 4:55 pm

    As someone else commented… I had heard about a new drug that DID still cause respiratory depression. It concerns me that there is conflicting information. Did some drug company influence the information being released?!?

    When/if this drug is put on the market, it will be a brand name drug when most of us are paying for generics. I have to be mindful because I have multiple health conditions. I take tramadol now and when I used to be able to get a 90 day supply, I now can only get 30 days at the local pharmacy (because of my insurance). The price jumps as a result.

    We need reforms so people can afford their medications. I can’t be excited about something new because “new” generally means “unaffordable.”

  7. Heidi at 2:16 pm

    I would be so willing to be a trial subject. I’m suffering from CRPS/RSD along with other chronic pain.

  8. Sandy Auriene Sullivan at 10:36 am

    Suggestion for those suffering under new guidelines. I would be suffering very much had we not changed my medicine from oxymorphone [opana] to oxycodone [oxycontin/break thru med] the bioavailability of Opana is very low. Meaning, I was suffering despite a higher dosage because it went straight thru me, even the IR med. Turns out it isn’t just me. After 3 years of Opana was able to change and lower my equivalent dose in doing so. Otherwise my doctor was going to reduce me based on the guidelines. I did tell my doctor while we discussed it; that the guidelines are only a directive [especially if the state doesn’t adopt it as they have to do now] – not a mandate and your best judgement is still required.
    My dose of oxycodone, tho lower than 3 years ago; is working.
    Ask your doctor instead of lowering your medication if he can switch you instead. A change in medication does help. I manage my chronic anxiety disorder very similar and can lower a dose by changing from one benzo to another type in the same class.

  9. Mary s at 9:58 am

    If you needs to do tral test for chronic pain suffers. Please sign me up!

  10. MichaelL at 7:54 am

    The biggest hope is that it could be fast-tracked into use. Sadly, methadone, Demerol, and Tramadol were pushed as being less addictive when they were developed. Now, getting Tramadol requires that a pain contract be signed! I fear it my be another SNAFU! SOS!

  11. flyingcars at 12:28 am

    Don’t get too excited, this is a promising drug candidate in MICE! I read conflicting reports on it’s respiratory depression abilities, but any decrease is a win. But it hasn’t been tested in other animal models yet. There is a very long way to go before this drug is tested in people, if it even makes it that far!
    I’ve read about “breakthrough” experimental drugs over the last 20 year’s, & most go nowhere, so I take drug research, with a grain of salt. And my insurance probably won’t cover if it ever makes it to the market in 10 or 15 year’s.

  12. Sharon coffman at 11:37 pm

    I think it would be wonderful if we could function normally. Spinal stenosis and a myriad of other problems makes each day difficult.

  13. Jo at 3:13 pm

    If they are just working on mice, they are years and miles of red tape away from humans.
    But God bless them for working on this!
    Here’s to any success in laws and breakthroughs that will help the chronic pain world move back into the real world!

  14. Joan at 2:57 pm

    Doesn’t it take like ten years to actually get on the market?

  15. Christine jacoby at 2:02 pm

    Yes please too would love to be in trials for this med since I have only found relief in one med after sixteen years, if I had a choice or even better effective med then I would have closer to a normal life(even in wheelchair).
    The choices we have are all too similar so a new approach maybe will help me more.

  16. Steve Goldie at 1:24 pm

    If you want a test subject I would happily volunteer

  17. Renee Mace at 12:35 pm

    Where do I sign up for any clinical trials, I am desperate, I am not on enough pain medication any more because of the CDC’s Guidelines and my health is at risk. Since they lowered dose, I am prediabetic. I use to be able to walk my dogs once in a while or see my doctors without going into the worse pain ever and getting sick from it including my blood pressure. Other than having Central Pain Syndrome in both my legs and dealing with the horrible pain that comes with it, my health was good, now that I am not dosed correctly, my health has been deteriorating swiftly. Please let me be one of your patients for testing your new pain medications before it is to late for me to either die of a heart attack/stroke or become from prediabetic to full blown diabetic.

  18. Katie Olmstead at 11:29 am

    What an exciting potential breakthrough. I hope this is the real thing, at least for some people, along with the mice.

  19. Lora S... at 11:21 am

    That’s Good News! When will it be ready for Clinical trials???
    I would like to volunteer for Human study!!! How Can I Find Out???

  20. Joan Hamm at 9:14 am

    My body doesn’t always respond correctly to some pain medicine. I think it is just one part of the medicines that doesn’t work… But I don’t know until I sample it. The pain of RSD /Crps is unbearable without pain medicine. In the beginning of my disease we tried several meds until I finally said this works… It eases the pain so I can function and try to do good work for others. Volunteer etc. When I can do so. RSD has to be listed as the worst pain list such as Cancer. Can be even more pain than other top pain diseases. My meds are common for RSD patients. I am open to a miracle med that eases the pain attacks that are UNBEARABLE!!!

  21. Carla Cheshire at 8:44 am

    When will it be ready for drug trials? I hope this will be a real breakthrough!

  22. Layla Rose at 8:39 am

    This is actually very encouraging news. When are there going to be drug trials for people? That’s what I’d like to know. I also wonder if I’d still get my paradoxical stimulant effect I normally feel from opioid meds, as that is often, in addition to pain relief, the only other thing that keeps me up and out of bed for any length of time?

  23. Kathy at 8:19 am

    Are there any clinical trials for humans yet? How can I find out? I would like to be a volunteer for a human study.