In Vitro Approach to Evaluating Opioid Receptor Subtype Specificity
Abstract
Reported potencies of opioid compounds were derived from in vitro, in vivo, and ex vivo methods in various model species for all the experiments that were conducted. In this study, a human receptor-expressing cell system was used to measure the potency and efficacy of carfentanil (a known ultra-potent opioid) and 4-chloro-N-[(2Z)-1-[2-(4-nitrophenyl)ethyl]piperidin-2-ylidene]benzene-1-sulfonamide (W-18, a suspect opioid that has received much attention as a public health concern). This system demonstrated the ease and efficiency of using a set of cell-based tools to screen for opioid activity and specificity for future compounds of interest and suspect or unknown opioid or opiate compounds. Carfentanil was more specific for the -opioid receptor (MOR) than previously thought, but its low median effective concentration indicated that it could have off-target effects at physiologically relevant concentrations, which could potentially lead to toxicity. W-18 was inactive at all four human receptor subtypes (delta-opioid receptor, kappa-opioid receptor, MOR; and opioid-like receptor 1), which refutes reports that W-18 is an ultra-potent opioid (10,000 times more potent than morphine). Although this study does not account for reported toxicity, it does rule out the opioid system as the culprit receptor.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2017
- Accession Number
- AD1111026
Entities
People
- Andrew J. Walz
- Michael G Feasel
- Theodore S. Moran
Organizations
- Edgewood Chemical Biological Center