Synthesis and pharmacological characterization of ethylenediamine synthetic opioids in human μ-opiate receptor 1 (OPRM1) expressing cells.

ABSTRACT: Opioids are powerful analgesics acting via the human μ-opiate receptor (hMOR). Opioid use is associated with adverse effects such as tolerance, addiction, respiratory depression, and constipation. Two synthetic opioids, AH-7921 and U-47700 that were developed in the 1970s but never marketed, have recently appeared on the illegal drug market and in forensic toxicology reports. These agents were initially characterized for their analgesic activity in rodents; however, their pharmacology at hMOR has not been delineated. Thus, we synthesized over 50 chemical analogs based on core AH-7921 and U-47700 structures to assess for their ability to couple to Gα_i signaling and induce hMOR internalization. For both the AH-7921 and U-47700 analogs, the 3,4-dichlorobenzoyl substituents were the

SUBMITTER: Hsu T 

PROVIDER: S-EPMC6704399 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature