Researchers Develop New Painkillers, Reduce Overdose Risk

Researchers Develop New Painkillers, Reduce Overdose Risk

By Staff.

In an effort to develop safer opioid painkillers, scientists are investigating new opioid medications that reduce pain on par with morphine, but do not affect breathing – the cause of opiate overdose.

Research published in the journal Cell shows that a range of compounds can deliver pain-blocking potency without affecting breathing.  The study describes a method of making safer opioids without the risk of overdose death, which has been associated with opiates like oxycontin, heroin and fentanyl.

Study leader from The Scripps Research Institute (TSRI) Professor Laura M. Bohn, Ph.D., said the study builds on two decades of research by Bohn and her colleagues, who long questioned whether the painkilling pathway, called the G protein pathway, could be decoupled from the breathing suppression pathway, called the beta-arrestin pathway.

“One of the questions we had was how good we can get at separating out the pathways, and how much separation do we need to see analgesia without respiratory suppression,” Bohn said.

For the study, the Bohn worked closely with TSRI chemist Thomas Bannister, PhD, to develop new potential drug molecules; they then tweaked their chemical structures to systematically vary the “bias” between the two pathways-G protein signaling and beta-arrestin recruitment.

The group developed more than 500 compounds in the past six years, and they found more than 60 that showed bias between signaling assays. They then selected six compounds to represent a wide range in the degree of bias (from those that preferred barrestin2 recruitment to those that almost exclusively preferred G protein signaling) and determined their overall potency for inducing analgesia and respiratory suppression in mouse models.

The researchers found that the new compounds could indeed enter the brain-and all of the compounds were as potent, if not more so, than morphine. The compounds that were less able to promote barrestin2 associations in cells were also less likely to induce respiratory suppression in mice.

In contrast, the painkiller fentanyl was shown to prefer receptor-barrestin2 associations and also had a more narrow safety margin. In short, the fentanyl dose needed to alleviate the perception of pain was closer to the dose that suppressed breathing, which may be why fentanyl is more likely to trigger respiratory suppression at low doses. Fentanyl is a powerful pain killer, but one with a narrow therapeutic window and a history of overdoses. While this issue requires more research, “this at least brings into question whether this may be part of the reason,” Bohn said.

Bohn explained that separating the receptor’s ability to engage in the two pathways can provide a way to separate desired drug effects from side effects.

“I think what we have done here is shown that bias isn’t all or none-that there is a spectrum.” That suggests an opportunity to expand the “therapeutic window,” or the range of doses at which a drug may be administered safely, she said.

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Authored by: Staff

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Joel Stegner

I was hurt while demoing a nuclear facility owned by the government where they made plutonium fuel rods for our nuclear submarines they cut prices on safety and I got hurt badly and had three back operations and I cannot get any pain pills for it and I have proof beyond a shadow of a doubt that I’m in pain how come when an NFL player gets hurt they take him right to the locker room and they have a syringe of Demerol and a bottle of Vicodin just waiting for him and there’s no questions asked at all I know a few ball players and I know how the system works. I was doing my job making the environment better since it was radioactive and people were dying over it and I just get kicked to the curb why is it like that ?

Tim Mason

Nucynta is tapenadol. It is not a cannabis drug. Not related to cannabis at all.

Leslie Meadows

TIM: That drug they sent you is synthetic cannabinoid,treatment for Neuropathic pain supposed to be better than the drug you’re on double blind tests show.

Leslie Meadows

ALLISON:Why did you not look up drugs that equal what you r on & tell your doc?

Julie C.

Tim Mason:

Thank you so very much for your enlightening comments. Let us hope more consumers and government agencies realize that this article is not telling us anything “new”.

I, too, experienced an identical response to both IR and ER Nucynta. The horrific headaches were immediate and relentless!!

Likewise, my trial on Cymbalta was also a failure. I have a sensitivity to all serotonin and norepinephrine neurotransmitter-type medications; myoclonus (twitching) occurs shortly after starting my first dose. In an effort to prevent a permanent condition, I must discontinue right away.

I fear any “new” pain meds on the market will only continue to be reformulated SSRI/SSNI/kitchen sink meds, exactly as this article attempts to applaud. Yet we need more consumers like yourself who so eloquently pull the curtain away from all the smoke-and-mirrors.

Not to mention, the cost of all of these “new” [antidepressant] “pain meds” is huge! And that is only “if” a consumer has (private) PPO health insurance plans to cover them. Best of luck to those limited to Medicare or Medicaid coverage. . .

For the last 3 years, consecutively, I have been prescribed “traditional” opioids (Norco or Percocet for break-through pain; OxyContin for extended release coverage) for relief from the debilitating pain I suffer attributed to severe Rheumatoid Arthritis. I can honestly claim that I experience zero side-effects from these no-nonsense [“clean”] pain meds. I wish the same could be said for the 9+ trials of DMARD/Biologics (injectable/infusion treatments for RA) over 3 years, that have failed me.

My PM doc and I both would prefer Opana IR (not Extended Release, to be clear) in light of the acetaminophen-load of the aforementioned. However, my pharmacy can no longer order this legal medication in light of both the CDC/DEA dictatorship and those whose abuse before me are causing the chronic pain community to suffer their punishment and consequences.


These earlly drug news articles never talk about the leading side effects or what existing drugs they are similar to (in their methods of workinf on the body). Thanks to the informwd readers for clearing that up.

Tim Mason

I do not use alcohol. No beer, wine or liquor. This is just a head-up for those going to PM visit post New Years.
I saw a patient denied his medication recently. As I set in the waiting room he was leaving with his wife or significant other. The man appeared to be in his mid 50’s.
I heard him state. “They are not going to do this to me. I’ll find another doctor. Hell, all I had was a bottle of wine last night”
Of course I do not know if it was on his breath or in his UDS but we all now alcohol and narcotics do not mix. IMO-This man was foolish as risked not only his life but the practice in losing it’s license if he overdosed.

Just thought I would drop that here.

Tim Mason

” why is it that I don’t get a nabilone supply when I pick up my prescription”
I got 2 Naloxone injectors earlier in the year. My records were reviewed by an “outsider” and I my PM clinic was required to overnight them to me.


I cannot take morphine and we cronic pain suffers take our pain meds the rite way and I am a news watcher and I have not seen on the news anybody dying of pain meds but herion fentinol cocaine I see all the time, it’s [edit] to attack all cronic pain sufferers and lower there pain meds I was doing ok pain level was 7 or lower but now since this new pain doctor I’m going to see it taking a one size fit all approach and dropping all pain suffers to 65mg a day so stupid I have now been through 6 failed lower back operations damage nerve scar tissue on nerve 5 deterioration disc upper back 3 severe multiple bone spurs sticking me in my nerves and 2 bulging disc in my neck and another bulging disc in my lower back rite under my 2 cages at L4 L5 and one cage is coming out I need both kneese replace lyme disease seep in my brain I get very severe headaches and there is noway 65mg going to help I’m now in to much pain I must keep laying down on couch in so much pain what little quality of life I had is GONE😠 IM now looking into a different pain doc out of the state of newjersey just to strick and the doctors do not care how much I suffer. It’s just dispickable what there doing to all cronic pain suffers.

Tim Mason

Serotonin receptor signaling and regulation via β-arrestins.

(PMID:20925600 PMCID:PMC4776633)

If you cannot take Cymbalta or Nucynta due to headache you probably can’t take these either.
I don’t mean to be negative, but it pays to research something to find out the facts.


What I want to know is if they are really so concerned about chronic pain opiate users like me, overdosing , why is it that I don’t get a nabilone supply when I pick up my prescription? The answer is that we are really not the problem and the powers that be are aware of this but chose to turn the other way.

Tim Mason

If this drug involves serotonin reuptake inhibition it can cause intracranial pressure to build up. This is a major problem with Nucynta in many patients. I took it for about a week and developed a major headache. I continued to take it for three additional days hoping this side effect mentioned in the product insert would go away. It did not. I called my physician and described what was happening and was advised to STOP taking it immediately.
It took three days for the headache to slowly diminish.
I think any new pain medicine should a certain number of people in the study that cannot take SSRIs like Nucynta and Cymbalta to see if this side effect is produced at several dosage levels.

Byron Hood

Why not allow chronic pain patients access to what already works? I urge you all to call or visit your elected officials! If you cannot talk with your US Representative or Senator, call the local office and talk to the District or Regional Director, or call the Washington office and talk to the Chief of Staff.

Steve M

As I wait in a packed full waiting room to see my pain mgmnt Doc I pray that there’s no disruption in my current care & pain medicine which allows me to get up & out to take care of myself alone.
I’ve suffered w/Crps upper/lower for 24yrs. I no longer allow any invasive therapies or procedures.
Only want quality of life for whatever I incur going forward.
This study & hopefully success in years of trials & maybe getting breakthrough and possibly a fas-trac designation could be the most important new med for us that experience chronic pain & human suffering each day.

Guess it would save lives for those who abuse as well, though I can’t be concerned about that personally.


New patents. Brand names. More money.

Sounds like big pharm’s answer to MMJ & kratom. Darn those plants! Doing it naturally & taking their hard bought drug sales!

Joanne Bodnar

Not in my lifetime 🤦🏻‍♀️


In December, my “pain management” NP will be taking me off Fentanyl /morphine and begin to transfer me to a drug called buprenorphine. Mostly to decrease their liability to overdose I presume. Not sure of the equivalence to what I’ve been using for the past twelve years. I can only hope it will work, as I have no choice in the matter.

David Cole

Well isn’t that wonderful, however it’s less than 1% of the population ever have a problem with not breathing, and it’s usually in a hospital setting with people who aren’t used to taking opiate pain medication or it affects people that are taking 4, 5, 6 different medications. So if they’re working on it now it’ll be 5,10 years before the FDA approves it, then the insurance companies won’t pay for it for another 10 years. Where I’m happy people are thinking about this now, they should have been thinking about it 30, 40 years ago.



Kathy C

Nothing new or “innovative” here. Having followed this “Research” for 2 decades now, this is another version of the Magic Bullet. It is rather frustrating that Site Editors are unaware of the progression, or the context of these over-hyped “Findings.” They have run into serious stumbling blocks with this line of “Research.” Of Course Publicizing this will contribute to funding and notoriety for the “Researchers” but not much for the people who experience pain.
I have little faith anymore in the progress of Science. No one paid attention when Pharma Industry insiders bribed Congress and moved their Insiders onto Regulatory Boards.
The Recycling movement has extended into the realm of Medicine, since there is nothing new. the reason there is nothing new is becasue the current Products are Profitable enough. Even the “Cure” for Opiate Addiction is Profitable. The Public is being Gas Lighted by the Pharma Industry, The occasional release of a PR Piece like this is targeted to to give the false impression of progress. we are seeing the end of Science, and Reason, yet no one at the Pain Report has caught on.

Steven Rock

I hope a drug will be produced without any addictive properties. We, as people with intractable pain, only want pain reduction without the side effects that some of the present opioids have. That will be a blessing for everyone. The only trouble with trying to create such a drug is having the insurance industry paying developers to stop any such research so they won’t have to pay for new and expensive drugs. This is how our healthcare system is run. By the very rich who’s only goal is to profit even at the expense of lives. Those who have no moral compass run the country and are running it into the ground, “for profits.”


How many years before it’s on the market? How many cpp patients will die by then? How many horrific side effects will it have? Opiates are relatively safe when utilized properly.


So,in other words, they’re looking to “develop” a “drug” that does what KRATOM already does NATURALLY. Got it….


Thank you for this article. My one question is, do they have a date when this drug will be ready for distribution to the public?

Michael p p flegel

About 10 years late I am afraid!