BPR1M97

Cell lines

HEK-MOP cells (human embryonic kidney 293 cells constitutively expressing the human mu opioid receptor), CHO-K1-NOP cells (Chinese hamster ovary cells expressing the human nociceptin-orphanin FQ peptide receptor), U2OS-MOP cells (human osteosarcoma cells expressing human MOP), and myc-MOP-expressing mouse pituitary AtT-20 cells

Preparation Method

HEK-MOP cells were cultured in high-glucose DMEM supplemented with 10% fetal bovine serum (FBS). CHO-K1-NOP cells were cultured in F12 medium containing 10% FBS. U2OS-MOP cells were cultured in McCoy's 5A medium with 10% FBS. AtT-20 cells were cultured in DMEM with 10% FBS. Cells were treated with BPR1M97 at concentrations ranging from 0.6nM to 1.9µM. Incubation times varied by assay: 30 minutes for the cAMP assay, 1.5 hours for the β-arrestin-2 recruitment and receptor internalization assays, and 0.5 hours of pre-treatment with dye followed by real-time monitoring for the membrane potential assay.

Reaction Conditions

0.6nM–1.9μM; 0.5-1.5h.

Applications

In MOP-expressing cells, BPR1M97 acted as a full agonist, significantly inhibiting cAMP production, activating GIRK channels, recruiting β-arrestin-2, and inducing receptor internalization. In NOP-expressing cells, BPR1M97 acted as a G protein-biased full agonist, inhibiting cAMP production but failing to recruit β-arrestin-2.

Animal models

ICR mice, formalin-induced inflammatory pain model in ICR mice, and chronic constriction injury (CCI)-induced neuropathic pain model in ICR mice.

Preparation Method

Mice were subcutaneously (s.c.) administered a single dose of BPR1M97. For thermal and mechanical nociception tests, behavioral responses were recorded at specified time points post-injection. For tolerance and dependence studies, mice received twice-daily injections for 5 days.

Dosage form

0.2-9mg/kg; s.c.; Single or twice-daily injections for 5 days

Applications

BPR1M97 produced potent, dose-dependent antinociception in acute thermal, acute mechanical with efficacy comparable or superior to morphine. BPR1M97 caused significantly less respiratory depression, cardiovascular inhibition. BPR1M97 also induced conditioned place preference (reward effect) but with lower hyperlocomotor activity.

References:
[1] Chao PK, Chang HF, Chang WT, et al. BPR1M97, a dual mu opioid receptor/nociceptin-orphanin FQ peptide receptor agonist, produces potent antinociceptive effects with safer properties than morphine. Neuropharmacology. 2020 Apr;166:107678.