I’ve heard stories from EMTs of finding someone who OD’d and the EMT having to give them multiple doses of narcan.
My understanding is the u-opioid receptor is the one that causes respiratory depression. Naloxone has a stronger binding affinity for the u-opioid receptor than fentanyl, so it should displace fentanyl from the receptor.
A single administration of naloxone at a relatively high dose of 2 mg by intravenous injection has been found to produce brain MOR blockade of 80% at 5 minutes, 47% at 2 hours, 44% at 4 hours, and 8% at 8 hours.[72] A low dose (2 μg/kg) produced brain MOR blockade of 42% at 5 minutes, 36% at 2 hours, 33% at 4 hours, and 10% at 8 hours.[72] Intranasal administration of naloxone via nasal spray has likewise been found to rapidly occupy brain MORs, with peak occupancy occurring at 20 minutes, peak occupancies of 67% at a dose of 2 mg and 85% with 4 mg, and an estimated half-life of occupancy disappearance of approximately 100 minutes (1.67 hours).[73][74]
So at 4mg, the peak receptor occupancy is at 85%. But what happens if someone takes an extremely large dose of fentanyl like 20mg or more? Is naloxone enough to block the receptors and prevent death by respiratory depression?