Narcotic dosage and central nervous system opiate receptor binding.

Increasing doses of lofentanil (0, 0.08, 0.16, 0.31, 0.63, 1.25, 2.50, 5.00, and 10.0 micrograms/kg), a potent long-acting narcotic, were administered intravenously to rats to examine the relationship among narcotic dosage, degree of analgesia (inhibition of tail withdrawal reflex), anesthesia (no response to bone-crush injury), and central nervous system (CNS) opiate-receptor occupancy (inhibition of [3H] sufentanil binding). Our results demonstrate that increasing doses of lofentanil produce increasing analgesia and anesthesia and eventually complete opiate receptor occupancy. Analgesia occurs with doses of lofentanil (0.31 micrograms/kg) that result in levels of CNS opiate-receptor binding too low to be measured and anesthesia occurs with doses of lofentanil (1.25 micrograms/kg) that produce occupancy of about 25% of the available opiate receptors in subcortical areas and cortex. These findings in rats cannot be applied to narcotic usage in humans, but the data do indicate that in rats a dose eight times the anesthetic dose of lofentanil is needed to saturate virtually all available CNS opiate receptors (10.0 micrograms/kg). Whether saturation of most or all available CNS opiate receptors during narcotic anesthesia is of clinical importance remains to be determined.