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. Author manuscript; available in PMC: 2024 Jul 1.
Published in final edited form as: Nat Neurosci. 2023 Jun 8;26(7):1229–1244. doi: 10.1038/s41593-023-01350-3

Extended Data Fig. 4 |. Pharmacological and in vivo characterizations of RBC1HI.

Extended Data Fig. 4 |

a. Molecular structure of RBC1HI. b. RBC1HI enzymatic inhibition of HDAC1,2,3 (‘HDAC3’=free versus HDAC3 bound to NCOR2) demonstrating highest specificity to HDAC1 (n = 3 replicates; (AUC one-way ANOVA: F3,8 = 191.1, p < 0.0001; Tukey’s m.c. HDAC1 vs HDAC2 q = 11.55, df=8, p = 0.0002; HDAC1 vs free HDAC3 q = 17.22, df=8, p < 0.0001; HDAC1 vs HDAC3/NCOR2 q = 16.21, df=8, p < 0.0001; HDAC2 vs free HDAC3 q = 17.22, df=8, p < 0.0001; HDAC2 vs HDAC3/NCOR2 q = 16.21, df=8, p < 0.0001). c. Plasma bioavailability of RBC1HI at 3 or 10 mg/kg and with intraperitoneal versus oral administration, demonstrating longer bioavailability with the intraperitoneal route. d. Brain bioavailability of RBC1HI with the aforementioned administration doses and routes, demonstrating prolonged drug presence with the intraperitoneal route. Brain to plasma concentration ratios over time. Dose-dependent circulating RBC1HI bioavailability as measured by plasma concentration and brain concentration over time (3 mg/kg i.p.; n = 3 male C57BL/6 mice per time point). e. RBC1HI (3 mg/kg intraperitoneal) did not promote place preference as seen with morphine (6 mg/kg subcutaneous). f. 3 mg/kg RBC1HI does not affect locomotor activity up to two hours after administration. Values are represented as mean ± SEM ****p < 0.0001.