New research is expected to develop opioid analgesics without respiratory risk
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October 20 09:10:11, 2023
On November 20th, the opioid pain reliever is very effective in relieving pain, but it also leads to a higher risk of addiction. Eventually, the medication will be inhibited due to overdose, and even the breathing will stop. Now, in a new study, researchers from the Scripps Research Institute in the United States have discovered a way to separate these two effects, pain relief and respiratory depression, to make them effective. There are no opportunities for analgesics that pose a risk of respiratory failure. The results of the study were published in the November 16, 2017 issue of Cell, entitled "Bias Factor and Therapeutic Window Correlate to Predict Safer Opioid Analgesics."
Opioids inhibit pain by binding to specific receptors in the brain; these same receptors also cause respiratory depression. However, the way these receptors regulate pain and breathing may be completely different. Studies using mouse genetic models have suggested that avoiding activation of a particular signaling pathway results in a more beneficial response to morphine (resulting in pain without respiratory effects). The researchers then explored whether they were able to create drugs that activate pathways associated with pain relief without activating respiratory-related pathways.
Dr. Nora D. Volkow, Director of the National Institute on Drug Abuse, said, “We are pleased to have discovered a potential new mechanism that will help to create safer alternatives to opioids that are unlikely to The side effects of overdose deaths associated with opioid abuse. We are excited that basic research on how opioids work in the brain has led us to develop this new approach, and we will be here The field continues to make key progress."
The separation of pathways after receptor activation is called biased signaling. This study suggests that as this degree of bias increases, the ability of opioids to relieve pain in mice without affecting respiration is also enhanced. Similarly, compounds that activate the respiratory pathway cause more respiratory side effects at lower doses. Ultimately, opioids with a larger bias factor have greater safety margins or therapeutic windows, opening up opportunities for drug intervention.
Dr. Laura M. Bohn, the author of the paper and the main investigator of the Scripps Research Institute, said, “In this study, we confirmed this bias, which we call biased agonism, not a kind of There is a phenomenon of all or nothing, but exists as a range. Therefore, if the degree of small deviation between different pathways in cell culture gives the living organisms the least benefit, then there is potential Chemically improving this signal bias and subsequently improving this treatment safety window."
It is unclear how these biased pathways affect other side effects of opioids, including addiction. However, this finding may represent a new direction in developing a safer alternative to current opioid analgesics.