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Histamine H₃ Receptor Antagonists: Preclinical Promise for Treating Obesity and Cognitive Disorders

Division of Neuroscience Research, Global Pharmaceutical Research and Development, 100 Abbott Park Road, Abbott Park, IL 60064

The histamine H₃ receptor is an attractive G protein–coupled receptor drug target that regulates neurotransmission in the central nervous system and plays a role in cognitive and homeostatic functions. Drug discovery efforts by numerous pharmaceutical companies have focused on the preclinical development of H₃ receptor antagonists for the potential treatment of attention-deficit hyperactivity disorder, dementias, schizophrenia, as well as obesity and sleep disorders. This receptor exhibits molecular, pharmacological, and functional heterogeneity that informs the preclinical development of effective antagonists. Herein, we describe the biological and chemical implications for developing H₃ receptor antagonists and their therapeutic potential as disclosed through animal models of cognition, sleep, and obesity.

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