S 38093

Catalog No.S8598

For research use only.

S 38093 is a histamine H3 antagonist/inverse agonist with a moderate affinity for rat, mouse and human H3 receptors (Ki = 8.8, 1.44 and 1.2 μM, respectively) and no affinity for other histaminergic receptors.

S 38093 Chemical Structure

CAS No. 862896-30-8

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Biological Activity

Description S 38093 is a histamine H3 antagonist/inverse agonist with a moderate affinity for rat, mouse and human H3 receptors (Ki = 8.8, 1.44 and 1.2 μM, respectively) and no affinity for other histaminergic receptors.
human H3 receptor [1] mouse H3 receptor [1] rat H3 receptor [1]
1.2 μM(Ki) 1.44 μM(Ki) 8.8 μM(Ki)
In vitro

In cellular models, the compound was 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). Among the four histaminergic receptor subtypes, S 38093 is selective for the H3 receptor, its binding affinity for H1, H2 and H4 receptors being negligible[1].

In vivo S 38093, a novel brain-penetrant antagonist/inverse agonist of H3 receptors, on AHN (proliferation, maturation and survival) in 3-month-old and in aged 16-month-old mice. In aged animals, S 38093 induced a reversal of age-dependent effects on hippocampal brain-derived neurotrophic factor (BDNF) BDNF-IX, BDNF-IV and BDNF-I transcripts and increased vascular endothelial growth factor (VEGF) expression. The effects of chronic administration of S 38093 were assessed on a neurogenesis-dependent “context discrimination (CS) test” in aged mice. While ageing altered mouse CS, chronic S 38093 treatment significantly improved CS. Chronic S 38093 treatment increases adult hippocampal neurogenesis and may provide an innovative strategy to improve age-associated cognitive deficits. S 38093 is found to be active at a mean pharmacological dose of 0.3–1 mg/kg p.o./i.p. in animal behavioral tests of working memory (Morris water maze in rats; spontaneous alternation and concurrent serial alternation tests in mice; delayed matching to sample in aged monkeys) and episodic-like memory (social and object recognition tests in rats; contextual discrimination task in mice). S 38093 also improves attention, executive functioning, and cognitive flexibility in MPTP-treated monkeys. Moreover, in line with its H3 antagonist/inverse agonist properties, S 38093 dose-dependently increases extracellular histamine levels in the prefrontal cortex and facilitates cholinergic transmission in the prefrontal cortex and hippocampus of rats after both acute and chronic administrations[2]. S 38093 was rapidly absorbed in mouse and rat (Tmax= 0.25-0.5h), slowly in monkey (2h), with a bioavailability ranging from 20 to 60% and t1/2 ranging from 1.5h to 7.4h. The compound was widely distributed with a moderate volume of distribution and low protein binding. The brain distribution of S 38093 was rapid and high[1].

Protocol (from reference)

Cell Research:


  • Cell lines: HEK-293 cells
  • Concentrations: 0.01-100 μM
  • Incubation Time: 1 h
  • Method:

    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.

Animal Research:


  • Animal Models: C57Bl/6JRj male mice
  • Dosages: 0.3, 1 and 3 mg/kg/day
  • Administration: p.o

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 288.38


CAS No. 862896-30-8
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1CC2CN(CC2C1)CCCOC3=CC=C(C=C3)C(=O)N

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