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

Description:

Opioid-induced respiratory depression is the primary cause of death due to overdose.  Opioid antagonism by naloxone (Narcan), the only FDA-approved drug to treat opioid overdose, causes severe withdrawal related pain and stress in resuscitation patients.  Therefore, there is a desperate need for drug targets that counter respiratory depression by opioids without producing such undesirable side effects.  Our studies reveal that selectively targeting of the oxytocin receptor with the neuropeptide oxytocin or non-peptide agonists is effective in preventing, reducing, and reversing opioid-induced respiratory depression.  In addition to countering opioid overdose, oxytocin is reported to reduce pain while also improving the ability of patients to cope with symptoms of withdrawal.

Based on these properties, oxytocin can be clinically beneficial in the following ways. 

First, oxytocin is FDA-approved for another indication and recent preclinical studies have shown that oxytocin is safe in non-pregnant individuals.  This means that FDA approval for other indications could be fast tracked compared to a drug not already proven safe in humans.  A solution quickly approved for individuals desperate for an opioid without dangerous side effects would benefit people that rely on these drugs for severe pain management.  The pandemic has contributed to an unprecedented number of opioid overdose deaths, which has not shown signs of slowing. 

Second, based on the properties mentioned above, oxytocin is a potential non-opioid resuscitation agent.  As a non-opioid, meaning it does not bind to opioid receptors, oxytocin would carry less stigma as it saves lives compared to alternatives on the market today. 

Third, oxytocin could be used in combination with Narcan to reduce withdrawal-related side effects of opioid overdose reversal.  Narcan would preferentially be countering opioid actions, whereas oxytocin would counter a combination of side effects from both opioids and Narcan.  This would help resuscitation patients who presently experience sever pain and stress when opioids are withdrawn. 

Fourth, oxytocin has the potential to be used alone to reduce pain.  However, opioids are the most effective way to treat severe pain.  Instead, oxytocin can be used in combination with opioids to prevent their dangerous side effects.  Oxytocin given with an opioid would not only reduce the likelihood of overdose at high opioid doses, but could be used to reduce the opioid dose given for pain relief.  A stable oxytocin analog could also be compounded with serially reduced doses of opioids to tailor this effect to individual patients.   

Taken together, there are many ways targeting the oxytocin receptor can combat the opioid epidemic, which has shown no signs of slowing down during the pandemic. 

 

Patent Information:
For Information, Contact:
Sean Thompson
Sr. Licensing Associate
Office of Technology Commercialization
(210) 450-8756
thompsons3@uthscsa.edu
Inventors:
Glenn Toney
Allison Brackley
Keywords: