data + articles · 2 listed
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Servier, the French pharmaceutical company, developed S 38093 as a histamine H3 receptor antagonist meant to work alongside existing Alzheimer's drugs rather than replace them, stimulating hippocampal neurogenesis and boosting acetylcholine release in a way that looked synergistic with donepezil in aged-mouse models. That preclinical promise carried it into two large international Phase II programs, one alone and one combined with donepezil, enrolling more than 1,300 patients with mild-to-moderate Alzheimer's disease across roughly 40 countries. After a year of dosing at three different levels, none of the arms beat placebo on cognition, function, clinical global impression, or caregiver burden, and treated patients had more falls than those on placebo; Servier discontinued the program on efficacy grounds despite the drug being otherwise reasonably well tolerated.
- stimulated hippocampal neurogenesis in aged-mouse models
- improved spatial working memory in the Morris water maze in rats
- showed a synergistic memory effect when combined with donepezil in middle-aged mice
- reasonably well tolerated across a large Phase II safety database
- more falls reported in treated patients than in the placebo group
- no cognitive or functional benefit over placebo in the pivotal Phase II trials
- program was discontinued, so no long-term human data beyond the trial period exists
- S 38093's Phase II Alzheimer's program enrolled over 1,300 patients across roughly 40 countries, a scale most experimental H3 antagonists never come close to reaching.
Mechanism
H3 receptor /inverse ; stimulates hippocampal and increases and release, and showed a synergistic memory-enhancing effect with the inhibitor donepezil in aged-mouse models.
Safetyrisks and cautions, not medical advice
Falls were the one adverse signal that separated from placebo. Across two Phase 2 programmes covering more than 1,300 patients in about forty countries, dosed at 2, 5 or 20 mg a day for a full year, the drug was otherwise described as reasonably safe, and Servier stopped it because no dose beat placebo on cognition, function, global impression or caregiver burden. A falls signal reads worse than it sounds in a dementia population, where a fractured hip often changes the course of the illness outright.
History
Developed by Servier through the 2010s; advanced into two large Phase II trials in mild-to-moderate Alzheimer's disease (as monotherapy and combined with donepezil) enrolling over 1,300 patients across roughly 40 countries; discontinued after failing to separate from placebo on any cognitive or functional measure after a year of treatment.
Subjective profileweighing the evidence above
A mechanistically interesting neurogenesis-promoting H3 antagonist that a large, well-run Phase II program still could not turn into an Alzheimer's benefit.
Resources
This entry is here for reference.
Research
- 1.In vivo pharmacological profile of S 38093, a novel histamine H3 receptor inverse agonist
- 2.S 38093, a histamine H3 antagonist/inverse agonist, promotes hippocampal neurogenesis and improves context discrimination task in aged mice
2 listed here; entry last updated July 2026
Reviews
My notesprivate to this device
FAQ
Why did S 38093 fail despite promising animal data?
In two large Phase II trials totaling more than 1,300 Alzheimer's patients, none of the tested doses outperformed placebo on cognition, function, clinical global impression, or caregiver burden after a year of treatment.
Was S 38093 unsafe?
It was reasonably well tolerated overall, though treated patients experienced more falls than those on placebo; the program was stopped for lack of efficacy, not primarily for safety.
Adverse effects
- more falls reported in treated patients than in the placebo group
- no cognitive or functional benefit over placebo in the pivotal Phase II trials
- program was discontinued, so no long-term human data beyond the trial period exists