New Non-Addictive Painkiller

[adamn1t (OP)]

Original story here               
http://www.iflscience.com/health-and-medicine/new-non-addictive-painkiller-may-provide-safer-alternative-opioids



A new painkiller made by adapting the body’s naturally occurring opioids could provide a safer, non-addictive alternative to current analgesic drugs, with far fewer side-effects than those produced by morphine.

Opioids are natural or synthetic compounds that bind to the opiate receptors in the brain and central nervous system in order to numb feelings of pain. At present, the most effective painkilling drugs are those that act on the mu opioid receptor (MOR), with morphine being among the most common of these. However, many of these substances also cause damaging side effects, negatively affecting breathing and motor coordination as well as being highly addictive.

Endogenous opioids – meaning those that occur naturally within the body – such as endomorphin help to biologically regulate pain, although most previous attempts to harness them for the production of new drugs have ended in frustration. This is largely due to their linear structure, which makes them somewhat unstable.

However, a team of researchers from Tulane University has managed to produce a number of endomorphin variants with improved stability and solubility, by converting them into a ring structure. When administered to rats these variations, or analogs, produced significant reductions in the six major side effects associated with morphine, at doses that yielded the same analgesic effects.

For instance, by placing the rats on a rotating rod and observing their ability to maintain balance, the researchers noted that subjects displayed impaired motor coordination after receiving morphine but not when they received these endomorphins. Additionally, they found that the rats’ breathing was not disrupted by the endomorphins as it was by morphine, while further tests showed that glial activation was also avoided by the new compounds.

Glial cells are involved in the amplification of pain and can become overactivated by morphine, meaning regular users often suffer from hyperalgesia, whereby their regular responses to painful stimuli are intensified without the drug. This contributes to the addictiveness of morphine, although rats were found to exhibit greatly reduced levels of hyperalgesia when treated with endomorphins instead.

While all of the endomorphin analogs generated some degree of reduction in side effects compared to morphine, one in particular – known simply as analog 4 – was found to be superior to all others. Among the reported benefits of this compound is a markedly decreased potential for abuse, highlighted by the way in which rats did not become addicted to it.

To test this, the rats were trained to press a button in order to receive analgesic drugs. When morphine was used in this experiment, rats continually increased the rate at which they pressed the button as dependence set in, although this effect was completely absent when analag 4 was used.

A report of these experiments has been published in the journal Neuropharmacology, and the researchers now hope to begin clinical trials using human subjects within the next two years.

[thetalkingasshole]

So if I become physically dependent on one of these new class of drugs
which how could you possibly not be producing opiates endogenously with chemical assistance
am I still considered a junky?

[DeadCat]

"it is't addictive?!!'  Thta sounds so famiiar. Where have I heard this before?

[Griffin]

I wouldn't mind taking this just in case there is a lawsuit against them where I can make money.

[AllNightLong]

"it is't addictive?!!'  Thta sounds so famiiar. Where have I heard this before?

I believe that is what Bayer said when they developed heroin as a morphine substitute.

[Snout]

I believe that is what Bayer said when they developed heroin as a morphine substitute.

Nice! This is my favorite opioid factoid ever!

[Jega]

http://www.journals.elsevier.com/neuropharmacology
That's the journal that this story is written about but I haven't found free copies of the full articles yet. In any case I don't buy this for one second! and...

I wouldn't mind taking this just in case there is a lawsuit against them where I can make money.

That's not the worst idea i've heard!

[adamn1t (OP)]

As with all new drugs a lot remains to be seen, but im all for it.

If they could make a drug that really can block pain without the negative side effects ti would be great.
If im reading this right it seem the rats dont experience much loss of motor function and might not be getting "high"
and i think that would def help with addictive nature of things.

Dont get me wrong i love traditional opiates and i dont think they will ever be replaced, but to have something that is safe and actually does something for pain could be really beneficial.

Like maybe an otc tylenol replacement, because fuck that shit. It seems to be more dangerous than beneficial.

[Zoops]

I believe that is what Bayer said when they developed heroin as a morphine substitute.

And tramadol, and oxycodone, and methadone, and probably a few others that fail to come to mind at the moment.

But yeah, as soon as I saw this thread topic, I was thinking, "this new drug is probably going to pretty reliably be a good high."

[Narkotikon]

Yeah, non addictive pain killers that actually work are a benefit to those in pain. I'm all for that. But I have a feeling that some doctors would only script for these new drugs, and only script for traditional opiates in the very worst cases, or possibly not at all.

It's the fact that it would possibly limit the use of traditional opiates that bothers me. It's already hard enough to get adequate pain control for a lot of people. Far too many IMO. What happens if this new drug isn't as effective as traditional opiates from a patient's standpoint, but the prescribing doctor thinks it is?

Kind of like how a lot of pain patients say reformulated OP OxyContin is nowhere near as effective as the original OG version, yet doctors insist it is.

I can just see too many problems with this. I think it will eventually limit treatment options even further for some doctors, and therefore their patients.

[robojunkie]

Endogenous, Exogenous, plant-based, animal-based, weird sea creature-based, whatever, if it binds to the MOR 1/2 then it is going to cause the development of tolerance and down regulation of said receptors.  It goes hand in hand, one cannot get the "good parts" without having the longer term shitty adaptation parts, because they are cause and effect.  No way around it, only maybe the rate at which it happens.

And yeah that's totally true, Baeyer company initially marketed Heroin® as a non-addictive morphine like cough suppressant (they must have known it was, or maybe they really were that naive that adding a couple esters to it would like totally change only the bad parts).

Also interesting, earlier on, before diacetylmorphine or any semi-synthetic opioids were produced, the hypodermic syringe was invented, I believe, in the late 1840s or early 1850s, and it was thought that injecting the morphine, whether IV, or SC, or IM, etc, would be non-addictive as it bypassed the stomach.  (You know, like stomach = appetite kinda = addiction, so no stomach, no addiction, I mean they didn't know jack about molecules and neurology back then, they didn't even know what benzene looked like yet, never mind morphine, and no idea that drugs like that had their action in the brain).

The only non-addictive pain killer that has ever existed and will ever exist is the much less specific killer, called death.  Death does kill pain, problem is it kills everything else with it.  Being kinda sarcastic, but its like saying you can flip a light switch and the light will turn on, but no electricity will go through it though.  Cause and Effect.  I spent a lotta lotta hours pondering biochem and neurology and pathways and synthetic chemistry with hopes of one day somehow being that one guy in a few billion that could come up with a full on opioid agonist that would never cause receptor down regulation, tolerance or withdrawal or any type of addiction even, other than simply the liking of it like a tasty cake you want tomorrow too.  Then I woke up and realized there is no free lunch in the universe. 

Wanna feel extra better super double plus good now?  Gonna pay the fucking piper later.  And double joke I guess on the poor fuckers that have to deal with severe physical nociception, cause fairness and all that isn't really of much interest to the universe either.  I don't think some of these researchers really understand what actually goes on just outside, just inside, at the receptor and way inside the brain cell when its MORs are continually stimulated by mu opioid agonists.  Unless artificial harmless retroviruses are designed that contain synthetic genes that code for the expression of excess MORs on neural membranes and the normal state of affairs to be somewhere along the lines of a perc30 half an hour after eating it (IR) (due to the now excessive MORs representing increased number of targets for natural endorphins/endomorphins/enkephalins, and hence a greater frequency of natural hits), there will NEVER be a successful and verified accurate non-addictive opioid painkiller.  Only weaker and weaker opioids, that have much less of a "subjective" high, but also much less of a "subjective" sense of being in horrible pain or extremely bored and malcontent.