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. 2022 Jun 23;13:3590. doi: 10.1038/s41467-022-31342-z

Fig. 9. Hot plate and GI transit efficacy studies after subcutaneous administration of AG10-L2-Nal and two doses of morphine.

Fig. 9

a Evaluation of AG10-L2-Nal (single subcutaneous dose; 35 μmol/kg) and naloxegol (single subcutaneous dose; 3.5 μmol/kg) efficacy in reversing analgesia, statistical differences were determined using one-way ANOVA followed by Tukey’s post hoc test F(3,20) = 510.4, P < 0.0001 and/or b opioid-induced constipation (OIC) caused by two subcutaneous doses of morphine (2 × 35 μmol/kg) in male Sprague-Dawley rats. The saline group received 0.9% sterile saline at 0 h, vehicle at 5 min, and another 0.9% sterile saline dose at 1.5 h. The control group received 35 μmol/kg morphine at 0 h, followed by vehicle at 5 min, and a second morphine dose (35 μmol/kg) at 1.5 h. All other groups received 35 μmol/kg morphine at 0 h, followed by naloxegol (3.5 μmol/kg) or AG10-L2-Nal (35 μmol/kg) at 5 min, and a second morphine dose (35 μmol/kg) at 1.5 h. The hot plate latency was measured after 2.5 h of the first saline or morphine dose at 55 ± 0.5 °C temperature. For the Gastrointestinal (GI) transit assay, 1 mL of charcoal meal was given by oral gavage 30 min after the first saline/morphine dose. GI transit was measured after 2.5 h of the first saline or morphine dose. Statistical differences were determined using one-way ANOVA followed by Tukey’s post hoc test F(3,20) = 301.8, P < 0.0001. All data are presented as mean (±s.d.) (*P < 0.05, n = 6 rats per group). Source data are provided as a Source Data file.