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. 2020 Oct 29;13:568641. doi: 10.3389/fnmol.2020.568641

FIGURE 6.

FIGURE 6

Systemic treatment with CYP46A1 inhibitor decreased central and peripheral 24S-HC. Mouse PK after single systemic administration of 30 mg/kg of compound 1 (A). Significant plasma 24S-HC reduction observed 8 h after compound 1 administration (B). Brain 24S-HC reduction observed between 4 and 16 h after CYP46A1 inhibitor treatment (C). Mouse PK after 3 days of BID administration of compound 1 at 15, 30, and 60 mg/kg doses (D). Significant plasma (E) and brain (F) 24S-HC reduction observed with every dose. Mouse PK after 3 days of BID administration of compound 2 at 30, 60, and 90 mg/kg doses (G). Significant plasma (H) and brain (I) 24S-HC reduction observed with every dose. All observations with compound 1 and 2 in the subchronic studies were made 4 h after last compound administration. Cpd 1, compound 1; Cb, total brain concentration, Cp, total plasma concentration, Cb, u, unbound brain concentration, Cp, u, unbound plasma concentration. *p < 0.05; ***p < 0.001; ****p < 0.0001.