Extended Data Fig. 5: GLP-1–MK-801 is devoid of hallmark MK-801-induced adverse effects.

a, b, Supporting data to study in Fig. 1a–h (vehicle (isotonic saline), n = 10 mice, 100 nmol kg⁻¹ MK-801 n = 10 mice, 100 nmol kg⁻¹ GLP-1 n = 10 mice, 100 nmol kg⁻¹ GLP-1–MK-801 n = 10 mice). a, Plasma alanine transaminase (ALT) activity. b, Plasma aspartate aminotransferase (AST) activity. Two samples were removed from vehicle group, i.e., one sample was non-detectable and for another sample the activity was a significant outlier (Grubbs test). c, Heart weights of mice in Extended Data Figs. 3d–g and 3o–s (vehicle n = 8 mice, 100 nmol kg⁻¹ MK-801 n = 8 mice, 100 nmol kg⁻¹ GLP-1 n = 8 mice, 100 nmol kg⁻¹ GLP-1–MK-801 n = 8 mice). d-j, Assessment of cardiovascular safety following chronic treatment of chow-fed lean C57BL/6 J mice with once-daily s.c. injections of 100 nmol kg⁻¹ MK-801 (n = 9 mice and 4 cages), 100 nmol kg⁻¹ GLP-1 (n = 10 mice and 4 cages), 100 nmol kg⁻¹ GLP-1–MK-801 (n = 10 mice and 4 cages), or vehicle (isotonic saline, n = 10 mice and 4 cages) for 14 days. On day 14, mice were anesthetized, and blood pressure and echocardiograms were recorded. One mouse was euthanized on day 12 in MK-801 group due to sickness. d, Schematic. e, Change in body weight. f, Cumulative food intake. g, Heart rate in beats per minute (bpm). h, Mean arterial pressure. i, Systolic blood pressure. j, Diastolic blood pressure. k, Rectal temperature on day 14 of mice from study in Fig. 1a–h. Data analysed by one-way ANOVA, multiple comparison, Bonferroni post hoc test (a-c and g-k) and two-way repeated measures ANOVA to assess main effects of treatment (e and f). Data represents mean ± SEM; ^*P < 0.05, ^**P < 0.01, ^****P < 0.0001. Detailed statistics are in Supplementary Table 1. The diagram in d was created using BioRender.

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