S 38093 is a brain-penetrant antagonist of the H3 receptor (Ki: 8.8/1.44/1.2 μM, for rat/mouse/human).

H3 receptor (rat):8.8 μM(Ki), H3 receptor (human):1.2 μM(Ki), H3 receptor (mouse):1.44 μM(Ki)

在细胞模型中，S 38093能够拮抗小鼠H3受体(KB: 0.65 μM)，并且能够抑制由H3激动剂引起的cAMP降低(KB: 0.11 μM)。在表达高密度H3受体的细胞中，S 38093对大鼠和人类H3受体表现为中等强度的反向激动作用（EC50: 分别为9/1.7 μM）[2]。

在年轻成年小鼠中，S 38093（0.3/3 mg/kg/天，口服，28天）显著增加了海马齿状回（DG）内前体细胞的增殖。S 38093（0.3 mg/kg/天）显著增加具有第三级树突的DCX+细胞数量。S 38093（0.3/1/3 mg/kg）显著提高老年小鼠海马DG中细胞的存活、增殖和成熟，相比于对照组。S 38093（3 mg/kg/天，口服，28天）提高了细胞增殖，并对细胞存活产生强烈影响，也增加了两种基因型的树突交叉点，仅在APPSWETG小鼠中从50至80有显著效果。在老年小鼠中，S 38093的长期给药（1/3 mg/kg/天，口服，28天）逆转了这种与年龄相关的BDNF-IX/IV/I转录本的减少。此外，与老龄对照组相比，S 38093在三个测试剂量（0.3/1/3 mg/kg/天）均增加了VEGF转录本[1]。

S 38093 is formulated in purified water.The context discrimination task consists of an 8-day contextual fear discrimination paradigm in which the mice have to learn to distinguish between a fearful shock context and a similar non-shock context. On day 1 the mice are only exposed to the training shock context, and on days 2-8 the mice are exposed to the shock and then non-shock context in that order each day. The mice are run through the context discrimination task starting at 10 am and ending at 2 pm and are then gavaged with vehicle or S 38093 at 4 pm each day. The drug and vehicle are always administered after behavioral testing to avoid possible acute effects of the drug on behavior. Learning is measured by the percent time the mice spent freezing and testing is terminated when percent freezing is consistently significantly different between the two contexts. The mice are tested after 29 days of drug treatment. Conditioning is conducted on one side of a Med-Associates shuttle box (ENV-010MC; 20.3?cm?×?15.9?cm?×?21.3?cm high) with a clear plexiglass wall, 3 aluminum walls and a stainless steel grid as a floor. Mouse behavior is recorded by digital video cameras mounted above the conditioning chamber. In training context A, mice are allowed to habituate in new cages outside the room and are then brought into the room in the new cages. The house fan and house light are turned on, the stainless steel grid is exposed, the plexiglass wall is up and a mild anise scent is used as an olfactory cue. The door to the sound dampening enclosure is shut for the duration of the trial. 180?s after the mice are placed in the training context, they are delivered a single footshock of 0.75?mA lasting 2?s. 15?s after the end of the footshock, the mice are placed back into their home cages. Non-alcoholic antiseptic wipes are used to clean the grids and catch trays in between trials. An hour later the mice are brought into the room in paper buckets and put into similar context B.The house fan and house light are turned off, the door of the enclosure is left ajar, plastic placemat sheets are put into the shuttle box to make a high-walled circular enclosure, the plexiglass wall is left down and a mild lemon scent is used as the olf