Opiate Receptor Binding Properties of Carfentanil
Abstract
Efforts to increase the safety margin of opiate-type drugs led to the discovery of the fentanyl series of compounds. These compounds are sufficiently potent to produce surgical anesthesia with few of the negative side effects associated with morphine, except for respiratory depression. Previous research demonstrated a pharmacological dissociation between the analgesic and respiratory effects of narcotics that is based on different types of the opioid receptor. This study assessed the relative potency and selectivity of one fentanyl derivative (carfentanil) for the putative MU, KAPPA, and DELTA, types of opioid receptor. Rat brain tissue homogenates were labeled at the MU, DELTA, and KAPPA receptor sites. Carfentanil's apparent affinity for each receptor was estimated from the concentration required to displace 50% of the specifically bound radioligands. Biphasic displacement curves were observed for each radioligand, which suggest high and low affinity binding sites. Carfentanil appeared equipotent in displacing the MU and KAPPA radioligands with IC5Os of 0. 7 and 100 pM, while displacing the DELTA radioligand with IC5Os of 0.8 and 40 NM. The results are discussed in terms of their significance for explaining the persistence of respiratory depression of the pharmacologic profile of the fentanyl series of compounds.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 1987
- Accession Number
- ADA187637
Entities
People
- Darrel Menking
- James J. Valdes
- Roy G. Thompson