Longer occupancy of opioid receptors by nalmefene compared to naloxone as measured in vivo by a dual-detector system

Surgical procedures usually involve the administration of narcotic drugs as anesthetics or adjuvants. To reverse the effects of anesthesia, opioid antagonists such as naloxone are commonly used. Due to its short lasting effects, patients receiving naloxone must be monitored carefully. Nalmefene, a pure opiate antagonist with a longer duration of action than naloxone, has shown promise in the reversal of opioid anesthesia. Methods: A simple dual- detector positron radiation detector system and [11C]carfentanil were used to compare the duration of blockade of cerebral mu opioid receptors by naloxone and nalmefene in eight normal volunteers. Carbon-11-carfentanil brain kinetics were monitored for 5 min and 2, 4, 8 and 24 hr after the administration of either nalmefene (1 mg or 1 μg/kg) or naloxone (2 mg or 2 μg). Blood samples were obtained at the same times for plasma determinations. Results: Clearance half-times from opioid receptors were 28.7 ± 5.9 hr for 1 mg of nalmefene and 2.0 ± 1.6 hr for 2 mg of naloxone. Brain clearance times were about 21.1 and 3.4 times slower than plasma clearance times for nalmefene and naloxone, respectively. Conclusion: These findings suggest that the prolonged effects of nalmefene are related to the slow dissociation of nalmefene from opioid receptors, which are not reflected in the plasma curve. This longer blockade of opioid receptors by nalmefene represents an advantage in the clinical management of postsurgical reversal of narcotic anesthesia and opioid side effects as well as the reversal of opioid overdose.