What if there was a method for ache sufferers to get all of the pain-relieving energy of opioids with not one of the addicting unwanted effects?
Opioids are one of many most powerful pain medications obtainable, however millions of Americans have struggled with prescription opioid misuse after getting hooked on the feelings of calm and euphoria they also induce. However new analysis suggests there could also be a method to chemically tailor opioids to scale back their addictive potential.
The primary wave of the opioid epidemic in the US started within the 1990s. By 2015, roughly 11.5 million Americans have been fighting prescription opioid misuse. The Facilities for Illness Management and Prevention estimates that nearly 500,000 people died from opioid overdose from 1999 to 2019. Current reviews have proven that this ongoing well being disaster has solely intensified through the COVID-19 pandemic. The U.S. reached a document 93,000 overdose deaths in 2020, a 29% improve from the earlier 12 months.
Many individuals with opioid dependencies report utilizing these medicine to relieve physical pain: Chronic pain treatment is a main reason behind opioid abuse. However there at present aren’t any equal medicines able to the offering the identical stage of ache reduction with out the potential threat of dependancy.
A less addictive opioid, nevertheless, might be an necessary software to cope with the opioid epidemic. I’m a physical chemist on this downside, and my analysis group used computational chemistry to examine how opioids like morphine will be redesigned to target specific pain regions without affecting the brain.
The biochemistry of opioids
There are lots of completely different lessons of opioids that modify in chemical construction. Nevertheless, all opioids comprise the identical sort of chemical group that dictates their biochemical exercise. Morphine, oxycodone and hydrocodone belong to the identical main class of epoxymorphinan opioids and share almost similar chemical structures.
Fentanyl, alternatively, belongs to the phenylpiperidineclass of opioids and appears fairly completely different.
Morphine and fentanyl have completely different chemical constructions however share a nitrogen group that endure a related chemical response within the bloodstream. Aaron Harrison, CC BY-ND
The chemical constructions of those molecules shall be a little bit of thriller should you haven’t taken an natural chemistry class earlier than. Nevertheless, we will simplify the image by specializing in what’s frequent between them. Each molecules comprise a nitrogen that’s a part of what’s referred to as an amine group. This group can change into positively charged through a chemical response that occurs in water-based environments such because the bloodstream.
This positively charged construction is the biochemically lively type of the opioid — it received’t have any impact in your physique till it good points this constructive cost. The constructive cost on the nitrogen helps these medicine bind to the goal web site the place the ache is originating and supply reduction.
The typical acidity level of the common individual’s physique gives perfect situations for morphine and fentanyl to change into positively charged. Because of this almost the entire drug that’s consumed shall be biochemically lively all through the physique. Whether or not it’s within the mind or on the web site of harm, cells all around the physique will really feel the results of the drug.
Making opioids less addictive
Lots of the addictive qualities of opioids are due to the feelings of calm and euphoria they induce within the mind. For situations like arthritis and wound and postoperative ache, nevertheless, these medicine want to goal solely the diseased or injured areas of the physique to present ache reduction. The query researchers face is whether or not it’s doable to restrict the impact of opioids to particular areas of the physique with out affecting the mind.
One recently proposed solution focuses on the acidity distinction between injured and wholesome tissue. Injured tissue is extra acidic than wholesome tissue due to a course of generally known as acidosis, the place lactic acid and different acidic byproducts produced by damaged tissue collect. Because of this an opioid may probably be altered to be positively charged and lively solely in injured tissue, whereas staying impartial and inactive in regular tissue. The drug could be biochemically lively solely at a greater acidity stage than present in wholesome tissue.
This principle was first explored utilizing fentanyl. Researchers discovered that introducing a fluorine (F) atom close to the nitrogen within the amine group can decrease the acidity vary by which fentanyl is lively, making it less doubtless to be lively on the regular acidity ranges of the physique.
Including a fluorine atom to fentanyl could make it less doubtless to be biochemically lively in wholesome physique tissues. Aaron Harrison
Including fluorine to fentanyl confirmed elevated opioid exercise within the extra acidic situations of injured tissue in contrast to wholesome tissue. This meant that the drug “turned on” solely in elements of the physique that wanted ache reduction. As well as, it confirmed a decrease in the severe side effects related to opioids, like addictive potential and abnormally decreased respiration charges, whereas nonetheless offering ache reduction.
My colleagues and I’ve just lately prolonged this framework to morphine. We confirmed that related fluorine substitutions may modify morphine’s lively acidity vary to particularly goal injured tissue. Provided that molecules in the identical class of opioids as morphine share related constructions, we consider this method would additionally work in different opioids like hydrocodone and oxycodone.
Including a fluorine atom to morphine could make it less doubtless to be biochemically lively in wholesome physique tissues. Aaron Harrison, CC BY-ND
Successfully treating ache with out placing sufferers in danger for dependancy stays a important downside in well being care. This method has been examined solely in lab settings and won’t be in pharmacies for a while, if ever. However chemically altering current opioids is a promising avenue in direction of growing medicine that alleviate ache with out inflicting dependancy.