Fig. 5: GTP-release-selective agonists enhance and prolong opioid-induced antinociception in mice. | Nature

Fig. 5: GTP-release-selective agonists enhance and prolong opioid-induced antinociception in mice.

From: GTP release-selective agonists prolong opioid analgesic efficacy

Fig. 5: GTP-release-selective agonists enhance and prolong opioid-induced antinociception in mice.

a, Hot plate (top) and tail flick (bottom) assays with muzepan1 (Muze1; 3 mg kg−1, intraperitoneal) and morphine (Mor; 12 mg kg−1, intraperitoneal) alone and combined. The calculated sum effect of both drugs (Σ) is shown for comparison. Right, mean (± s.e.m.) area under the curve (AUC). One-way ANOVA. b, AUC for 4 h hot plate (top) and tail flick (bottom) assays following treatment with different doses of morphine (Extended Data Fig. 6). Legend indicates the ED50 (with 95% confidence interval). c, Muzepan2 (Muze2; 12 mg kg−1, intraperitoneal) also enhances morphine (12 mg kg−1, intraperitoneal)-induced antinociception (analysis as in a). d, Muzepan1 (3 mg kg−1, intraperitoneal) prolongs fentanyl (Fent; 0.3 mg kg−1)-induced antinociception in male and female mice (analysis as in a). See Extended Data Table 4 for two-way repeated measures ANOVA analyses of time course data for a–d and the number and sex of mice in each assay (n = 6–14; individual mouse data are shown as symbols in the bar charts) as well as the results of post hoc ANOVA analyses for drug effect over time.

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