The opioid receptor triple agonist DPI-125 produces analgesia with less respiratory depression and reduced abuse liability.

ABSTRACT: Opioid analgesics remain the first choice for the treatment of moderate to severe pain, but they are also notorious for their respiratory depression and addictive effects. This study focused on the pharmacology of a novel opioid receptor mixed agonist DPI-125 and attempted to elucidate the relationship between the δ-, μ- and κ-receptor potency ratio and respiratory depression and abuse liability. Five diarylmethylpiperazine compounds (DPI-125, DPI-3290, DPI-130, KUST202 and KUST13T02) were selected for this study. PKA fluorescence redistribution assays in CHO cells individually expressing δ-, μ- or κ-receptors were used to measure the agonist potency. The respiratory safety profiles were estimated in rats by the ratio of ED₅₀ (pCO₂ increase)/ED₅₀ (antinocic

SUBMITTER: Yi SP 

PROVIDER: S-EPMC5519248 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature