Naloxone's dose-dependent displacement of [¹¹C]carfentanil and duration of receptor occupancy in the rat brain.

ABSTRACT: The continuous rise in opioid overdoses in the United States is predominantly driven by very potent synthetic opioids, mostly fentanyl and its derivatives (fentanyls). Although naloxone (NLX) has been shown to effectively reverse overdoses by conventional opioids, there may be a need for higher or repeated doses of NLX to revert overdoses from highly potent fentanyls. Here, we used positron emission tomography (PET) to assess NLX's dose-dependence on both its rate of displacement of [¹¹C]carfentanil ([¹¹C]CFN) binding and its duration of mu opioid receptor (MOR) occupancy in the male rat brain. We showed that clinically relevant doses of intravenously (IV) administered NLX (0.035 mg/kg, Human Equivalent Dose (HED) 0.4 mg; 0.17 mg/kg, HED 2 mg) rapidly displaced the sp

SUBMITTER: Kang Y 

PROVIDER: S-EPMC9018944 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature