Assessing the Activity of Synthetic Opioid AH‐7921 and U‐47700 Analogs in Cloned Human Mu‐Opioid Receptor Expressing Fibrosarcoma HT‐1080 Cells

Abstract

While important for their antinociceptive properties in medicine, opioids are commonly abused in America due to easily accessible opiate prescription pain medication. Classic opioids can induce adverse side effects such as gastrointestinal dysfunction and fatal respiratory depression, the latter of which is a key underlying factor contributing to the rising rates of lethality of opioid abuse. New synthetic opioids are emerging on the black market, many of which have not been characterized for structure activity relationships at human mu‐opiate receptors (hOPRM1). The rise of new synthetic opioids complicates the opioid crisis in America as they often escape the traditional illicit drug classifications established by law enforcement and may be more potent and lethal than conventional molecules. In this study, we developed a stable amino terminal HA‐tagged hOPRM1 expressing human fibrosarcoma (HT1080) cell line for determining the pharmacology of a panel of opioids analogs derived from synthetic opioids AH‐7921 and U‐47700. Expression of hOPRM1 was verified by Western blot and immunocytochemistry. Assessing the morphine response in this cell line revealed that morphine EC50 (39.3 nM) was comparable to published findings and were naloxone reversible, thereby validating this cell line. The analogs were assessed for their ability to suppress forskolin‐induced cyclic AMP (cAMP) levels in a hOPRM1‐dependent manner revealing a subset of structurally‐related analogs showing functional activity. The preliminary results found in this study indicate that some of the synthetic opioid analogs are likely to have abuse potential based on their ability to bind to and activate the human OPRM1 receptor.Support or Funding InformationThis project was supported by Award No. 2016‐R2‐CX‐0059, awarded by the National Institute of Justice, Office of Justice Programs, U.S. Department of Justice. The opinions, findings, and conclusions or recommendations expressed in this publication/program/exhibition are those of the author(s) and do not necessarily reflect those of the Department of Justice.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.