Histamine H3 receptor antagonists: Potential to address CNS deficits of memory, cognition, and attention

MEDI 260

Marlon D. Cowart, marlon.d.cowart@abbott.com, Neuroscience Research, R4MN, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064
The histamine H3 receptor is expressed in neurons where it plays an important role in negatively modulating the release of neurotransmitters, including histamine, acetylcholine, and dopamine. Antagonists of the receptor induce release of these transmitters, and importantly, are especially potent and effective in overcoming deficits in preclinical models assessing components memory, cognition, and attention. Results will be presented depicting the potency and in vivo efficacy of new series and standard compounds. In vitro SAR for the target (H3) and off-target sites (e.g. hERG, H1-4 receptors) will be analyzed, and profiles presented of specific example compounds, assessing for example general their CNS effects, PK properties, and overall drug-likeness.