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S 38093 is a brain-penetrant, orally active antagonist of H3 receptor, with K_is of 8.8, 1.44 and 1.2 µM for rat, mouse and human H3 receptors, respectively.

In cellular models, S 38093 is able to antagonize mice H3 receptors (K_B=0.65 µM) and to suppress cAMP decrease induced by an H3 agonist via human H3 receptors (K_B=0.11 µM). In cells expressing a high H3 density, S 38093 behaves as a moderate inverse agonist at rat and human H3 receptors (EC₅₀=9 and 1.7 µM, respectively).

S 38093 (0.3 and 3 mg/kg/d p.o., 28 days) significantly increases proliferation of progenitors in the DG of hippocampus in young adult mice. S 38093 (0.3 mg/kg/d) treatment significantly increases the number of DCX cells with tertiary dendrites. S 38093 (0.3, 1 and/or 3 mg/kg) significantly increases cell proliferation, survival, and maturation in the DG of hippocampus in aged mice relative to vehicle. S 38093 (3 mg/kg/d p.o., 28 days) increases cell proliferation and has a strong effect on cell survival, also increases the dendritic intersections in both genotypes (one-way ANOVA with repeated measure, p < 0.01), with a significant effect from 50 to 80 in APPSWE mice only. In aged mice, chronic administration of S 38093 (1 and/or 3 mg/kg/day p.o., 28 days) reverses this age-dependent decrease in BDNF-IX, BDNF-IV and BDNF-I transcripts. In addition, S 38093 at three tested doses (0.3, 1 and 3 mg/kg/d) increases VEGF transcripts compared to vehicle-aged group. In mice, S 38093 significantly increases ex vivo N-tele-Methylhistamine cerebral levels from 3 mg/kg p.o. and antagonized R-α-Methylhistamine-induced dipsogenia from 10 mg/kg i.p.

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