Histamine H3 receptor antagonists: preclinical promise for treating obesity and cognitive disorders.
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.
Division of Neuroscience Research, Global Pharmaceutical Research and Development, 100 Abbott Park Road, Abbott Park, IL 60064, USA. Esbenshade@Abbott.com
Timothy A
TA
Esbenshade
Gerard B
GB
Fox
Marlon D
MD
Cowart
D000818:Animals; D001288:Attention / Q000502:physiology; D003072:Cognition Disorders / Q000188:drug therapy*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006633:Histamine Antagonists / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D007175:Impulsive Behavior / Q000188:drug therapy; D008024:Ligands; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy; D008954:Models, Biological; D008958:Models, Molecular; D009474:Neurons / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy; D018100:Receptors, Histamine H3 / Q000378:metabolism / Q000502:physiology*; D012559:Schizophrenia / Q000188:drug therapy; D012893:Sleep Wake Disorders / Q000378:metabolism
D006633:Histamine Antagonists; D008024:Ligands; D018100:Receptors, Histamine H3