Next Gen Opioid Drugs Promise Pain Relief Without Side Effects – Health Rising – March 2016
Opioid based pain drugs have dominated the pain relief marketplace for years but their dominance has more reflected a lack of other options than anything else.
They’re quite effective at reducing acute pain but not so good at with chronic pain or with neuropathic pain.
They can produce a paradoxical hypersensitivity to pain and more mundane but still troublesome problems with constipation and itch.
Plus there’s the euphoria that abuse causes which can lead to addiction and a host of other problems.
Plus, patients responses to the drugs vary so widely that pain medicine has been called more of an art than a science.
Some people react well to one drug but poorly to a similar drug. They may react well to one dose but poorly to another.
New Pathways to Pain Relief
The breakthrough Dr. Pasternak believes is occurring began with the ability to “clone” and understand the genetic structure of the opioid receptors that dot our cells.
The receptors on our cells are the keys that unlock our cells potential.
Opioid drugs that lock onto opioid receptors in cells on our spinal cord and brain cause those cells to produce substances that reduce our pain.
It turns out that opioid receptor gene produces twenty different receptor types or “splice variants”.
These splice variants allow a single gene to code for multiple proteins depending on which portion of the gene is activated.
Further research indicated that these 20 different receptor types fall into three classes of opioid receptors.
It turns out that most opioid drugs lock onto one type of receptor (7TM) which activates pathways which reduce pain but which also cause most of the side effects we associate with our current regimen of opiate painkillers.
The figure [below] indicates that most of the opioid drugs used activate the wrong pathways.
The fact that the same drug can attach to different receptor types helps to explain why such variable responses to pain drugs are present.
If your cells happen to be littered with the MOR-1A receptor, for instance, you probably won’t have too many problems with methadone but if the MOR-1BA receptor dominates you can expect to experience lots of side effects.
A New Class of Opiate Pain Drugs
The solution to the opiate drug problem that’s staring pain drug makers in the face right now is to produce a molecule or drug that targets the opioid receptors that activate the good opioid pathways.
If they can manage to do that the news is very good indeed. Animal studies suggest that not only do these other pathways produce many fewer side effects but that they also appear to be better at reducing pain, particularly the hard to treat neuropathic pain.
At least three compounds have been produced, two of which are in clinical trials. The one Dr. Pasternak has developed called IBNtxA (3-iodobenzoyl-6β-naltrexamide) accomplishes a pain trifecta; it appears to be more effective against all three types of pain (inflammatory, neuropathic, thermal) than traditional opioid drugs….plus its side effects, with one possible important exception – are nil.
The one side effect that still appears to be present is tolerance. Tolerance occurs when more and more of a drug is needed to produce the same level of pain relief.
Dr. Pasternak said, however, that recent studies suggest that tolerance may have a ceiling; at some point, if enough of the drug is provided no more will be needed to reduce pain.
This may explain why pain patients don’t need ever-escalating doses of opioids: they have reached their ceiling of tolerance.
It would be interesting to study if such a “tolerance ceiling” is the same for all patients or if it also varies as much as other aspects of opioids.
Many groups, Dr. Pasternak said, are working hard to produce opioid drugs that activate these other pathways. IBNtxA – perhaps the most promising on the new slate of opioid drugs – is still being tested in laboratory animals. Two other drugs are in clinical trials.
In September 2016, PZM21 was shown in animal studies to deliver similar effects as opioids but without the side effects associated with them.