Fentanyl induces naloxone-resistant vocal cord closure: target validation and development of opioid overdose treatments using a peer-reviewed animal model
Active Project Grant Awarded Last action
- Award ID
- R44DA056267
- Recipient
-
Tmtrx, Inc. UEI VW2EHP9XKZ33
- Awarding agency
-
National Institute on Drug Abuse
National Institutes of Health, Department of Health and Human Services
- Obligated
- $4,804,558
Award facts
- Assistance listing
- 93.279 Drug Use and Addiction Research Programs
- Completion date 90% complete
- Originally
- Place of performance
- Portland, OR 97239, USA
Award details come from USAspending.gov.
Description
- Abstract
- According to the centers for disease control (CDC), synthetic opioids are currently the most common cause of overdose death in the U.S., and have increased opioid deaths by >500% from 2015- 2020. In 2020 alone, over 80% of the 69,700 opioid deaths were attributed to these synthetics (fentanyl). Despite the widespread availability of naloxone, the only FDA approved treatment for opioid overdose, deaths from fentanyl and fentanyl analogues (f/FA) continue to rise in parallel with increasing reports and pharmacological evidence of f/FA resistance to naloxone. High doses of rapidly injected f/FA cause airway obstruction from vocal cord closure (VCC) and severe chest wall rigidity (CWR) within 60-90 seconds, lethal effects that can persist for up to 10 minutes and appear to be resistant to naloxone. In contrast, morphine derived opiates (e.g. heroin) cause respiratory depression and mild muscle rigidity that is responsive to naloxone, but are not known to cause VCC in humans. The rapidly lethal phenomenon of VCC suggests unique pharmacological mechanisms underlying f/FA effects and may be a factor driving the dramatic increase in community overdose deaths. In support of this hypothesis, our published pharmacological data demonstrate f/FA, but not morphine or naloxone, have affinity for off-site targets that regulate these f/FA-induced effects. These in vitro data include f/FA concentrations that may be physiologically relevant to humans, based on available models of brain lipid concentrations for f/FA and by comparison with plasma levels in decedents of fentanyl overdose. Additionally, we have demonstrated in our published animal model that intravenous fentanyl induces VCC in
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| Original award | $324,196 |
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Quick answers
Who received award R44DA056267?
R44DA056267 was awarded to Tmtrx, Inc. by National Institute on Drug Abuse (National Institutes of Health) on September 15, 2022.
How much is award R44DA056267 worth?
$4,804,558 has been obligated on R44DA056267.
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