Oxytocin to prevent, reduce and reverse Opioid-Induced Respiratory Depression

Tech ID:

The use of opioids can result in lethal overdose caused by respiratory depression, but the mechanisms of opioid induced respiratory depression (OIRD) remain to be elucidated.  The only currently available, FDA approved, treatment for OIRD is the opioid receptor antagonist naloxone (Narcan).  The foremost limitation of using naloxone to combat OIRD is that it effectively interrupts the pain killing (analgesic) action of opioids, including Fentanyl, buprenorphine and morphine.  Our discovery overcomes these limitations by preventing and reversing OIRD while preserving the pain killing efficacy of commonly prescribed opioid pain killers.  Studies we began late in 2017 revealed that the neuropeptide oxytocin (OXT), which by itself reduces pain perception, is effective both in reducing/preventing as well as reversing OIRD. 

One of the most vulnerable populations to suffer lethal OIRD are patients with sleep apnea (SA).  Our efforts to discover the underlying cause of increased OIRD sensitivity in SA led to our discovery of OXT as an effective treatment against OIRD in general.  In regard to SA, it is noteworthy that patients with SA have been reported to have elevated cerebrospinal fluid (CSF) levels of endogenous opioids, which raised the possibility that combined actions of endogenous and exogenous opioids constitute a “double hit” that explains greater OIRD vulnerability in SA patients. This possibility is consistent with evidence that treatment with the opioid receptor antagonist naloxone not only improves symptoms of SA, but is effective against OIRD irrespective of whether patients do or do not suffer from SA. 

In anesthetized rats, our pre-clinical data take the form of direct recordings of electrical nerve impulses from the phrenic nerve, i.e., phrenic nerve activity (PNA).  The phrenic nerve is the primary nerve in all mammalian species, including humans, that causes rhythmic contraction of the diaphragm muscle and hence inspiration/inhalation.  Overall, data reveal that OXT is effective against OIRD both when administered to normoxic control rats as well as rats exposed to chronic intermittent hypoxia with hypercapnia (CIHHC), which is an established animal model of human SA.     


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Daniel Rafferty
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Glenn Toney
Allison Brackley
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