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 dru gs as anesthetics or adjuvants. To reverse the effects of anesthesia, opioid antagonists such as naloxone are commonly used. Due to its shor t lasting effects, patients receiving naloxone must be monitored caref ully. Nalmefene, a pure opiate antagonist with a longer duration of ac tion than naloxone, has shown promise in the reversal of opioid anesth esia. Methods: A simple dual-detector positron radiation detector syst em and [C-11]carfentanil were used to compare the duration of blockade of cerebral mu opioid receptors by naloxone and nalmefene in eight no rmal volunteers. Carbon-11-carfentanil brain kinetics were monitored f or 5 min and 2, 4, 8 and 24 hr after the administration of either nalm efene (1 mg or 1 mu g/kg) or naloxone (2 mg or 2 mu g/kg). Blood sampl es 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 cleara nce times were about 21.1 and 3.4 times slower than plasma clearance t imes for nalmefene and naloxone, respectively. Conclusion: These findi ngs suggest that the prolonged effects of nalmefene are related to the slow dissociation of nalmefene from opioid receptors, which are not r eflected in the plasma curve. This longer blockade of opioid receptors by nalmefene represents an advantage in the clinical management of po stsurgical reversal of narcotic anesthesia and opioid side effects as well as the reversal of opioid overdose.