The opioid crisis is a serious public health crisis in the United States. Mortality from opioid overdose increased by roughly ten times from 1999 to 2021. The primary cause of death is due to opioid-induced respiratory depression (OIRD). Currently, Naloxone and Nalmefene are actively used to reverse OIRD in emergency settings and by first responders. Both these drugs are µ-opioid receptor (MOR) antagonists, which compete with the opioid agents for the same receptors. As a result, they reverse the analgesia and also induce withdrawal, which has limited its application in the field.
Researchers at GW have found a new approach to overcome the drawbacks of MOR antagonists. Their work with leptin had shown promising results in treating OIRD. Melanocortin 4 receptor (MC4R) Is a part of the leptin pathways in the central nervous system. These pathways are different from the ones used by agents such as naloxone. MC4R involves many biological functions, such as energy homeostasis, cardiovascular function, drug addiction, pain perception, and mood. Setmelanotide, an MC4R agonist, is an FDA-approved drug for treating obesity. In the studies done on adult male C57BL/6J mice and adult male Sprague Dawley rats, Setmelanotide has been shown to increase respiratory rate and decrease the rate of sleep apneas by three times without affecting the analgesia.
Figure. A) Setmelanotide (Set) administered 15 minutes after morphine decreased the apnea index and duration of apneas and increased respiratory rate. RR, respiratory rate, Veh, vehicle; ** and *, p < 0.001 and < 0.05, respectively. B) Set administered 15 minutes after morphine has no effect on tail flick latency (a measure of reversal of analgesia).
Advantages:
Applications: