Fig. 7: Evaluating the potential partial agonistic behavior of AG10-L2-Nal and contribution of mu-opioid receptors in the CNS to analgesia and OIC.

a Hot plate latency, statistical differences were determined using Kruskal–Wallis test followed by Dunn’s multiple comparisons test, H = 9.769, P = 0.0021 b and gastrointestinal (GI) transit assays to evaluate potential partial agonistic behavior of AG10-L2-Nal. Hot plate latency or GI transit were checked 1 h after the subcutaneous dose of vehicle, morphine (35 μmol/kg), and AG10-L2-Nal (35 μmol/kg) in male Sprague-Dawley rats. Statistical differences were determined using one-way ANOVA followed by Tukey’s post hoc test, F(2,12)=354.4, P < 0.0001 c Hot plate latency, the significance of differences was measured by Kruskal–Wallis test followed by Dunn’s multiple comparisons test, H = 23.23, P = 0.0001 and d GI transit assays to evaluate the contribution of central and peripheral mu-opioid receptors to OIC. AG10-L2-Nal (35 µmol/kg; subcutaneous route, SC) and/or (0.35 µmol/kg equivalent to 88 nmol per rat; intracerebroventricular route, ICV) or vehicle (control group) was administered at t = 0 min. Morphine (35 μmol/kg SC) or saline (saline group) was administered at 10 min. The antagonists were administered 10 min before morphine to allow enough time to handle the animals during the ICV and SC dosing. Charcoal was given at 40 min. Hot plate latency and GI transit were measured at 70 min. Statistical differences were determined using one-way ANOVA followed by Tukey’s post hoc test F(4,20)=274.7, P < 0.0001. All data are presented as mean (±s.d.) (*P < 0.05, n = 5 rats per group). Source data are provided as a Source Data file.