In a recent study, researchers from Berlin developed a new generation of pain medications.
They used computer simulations to develop new opioids that will only work at sites affected by injury or inflammation.
These drugs could prevent brain- and gut-related side effects typically linked to opioids, and they have been shown to be successful in preclinical studies.
Opioids are a class of drugs with powerful pain-relieving properties.
They are mainly used to treat the pain associated with tissue damage and inflammation, such as that caused by surgery or cancer.
Common side effects associated with their use include drowsiness, nausea, constipation, dependency and, in some cases, respiratory arrest.
In the study, the research team aimed to develop new types of pain medications which will work without producing dangerous side effects.
They used computer simulations to develop two new opioids. In both cases, the researchers used fentanyl as the starting molecule.
The researchers hypothesized that tissues which are damaged or inflamed show a stronger interaction between ‘opioid agonists’ — the substances that elicit the pain-relieving effect — and the opioid receptors they bind to.
Their computer simulations suggested that this is due to an increased concentration of protons in inflamed tissues, which leads to lower pH values than in healthy tissues, resulting in acidic conditions.
Opioid molecules need to undergo protonation before they can bind to and activate opioid receptors.
The team used this knowledge to design two drugs that would only exist in their protonated state in the presence of inflammation.
This restricts opioid receptor activation to sites of tissue damage or inflammation, rather than receptors in the brain or gut.
The team suggests that their innovative design method provides a robust basis for a new generation of pain medications.
These drugs could help people. both to avoid the dangerous side effects of conventional opioids and to reduce complications
They would also help scientists stem the opioid crisis, a problem that is particularly evident in the United States.
The research team hopes to further develop these newly-designed drugs in order to make them available to patients.
They also plan to enhance their understanding of the molecular processes underlying the complex interactions seen in inflamed tissues, in the hope that they may be able to support opioid optimization through the insights they gain.
Ideally, their insights will also be beneficial for other drugs, such as those used to treat high blood pressure.
The research is published in Pain and Scientific Reports.
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Source: Pain and Scientific Reports.