In vitro activity: In cellular models, S 38093 is able to antagonize mice H3 receptors (KB=0.65 μM) and to suppress cAMP decrease induced by an H3 agonist via human H3 receptors (KB=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)

Kinase Assay: S 38093 is a novel brain-penetrant antagonist (inverse agonist) of the H3 (histamine H3) receptor with Ki of 8.8, 1.44 and 1.2 μM for rat, mouse and human H3 receptors, respectively.

Cell Assay: The cells (2 x 10⁶ per ml) were harvested and suspended in Hank's balanced salt solutions/HEPES (pH7.4) buffer containing 1 mM isobutyl-methylxanthine and 1mg/ml of BSA. The fluor 647-anti cAMP antibody solution (1 μl) was added to the cell suspension (100 μl) and 6 μl aliquots of this mix were dispensed in white 384-well microtiter plates. The cells were then incubated with 6 μl aliquots of S 38093 and/or the reference compounds (specific H3 agonist Imetit or antagonist Thioperamide) at increasing concentrations (0.01-100 μM), in the presence of forskolin (FSK, 0.5 μM final concentration) in order to preactivate adenylate cyclase. After a 1 h incubation at room temperature in the dark, the lysis buffer (0.35% Triton X-100, 10mM CaCl2, 50mM HEPES) containing LANCE EU-W8044 labeled streptavidin and biotinyled cAMP was added to the cells. After a 20 h incubation at + 4°C in the dark, plates were read on an microplate reader.