Recent advances in the development of histamine H₃ antagonists

Abstract

The histamine H₃ receptor is involved in the central and peripheral regulation of levels of histamine and other neurotransmitters (e.g., acetylcholine, noradrenaline, dopamine, serotonin and GABA), which sets it up as a target in the treatment of various CNS (e.g., depression, schizophrenia, ADHD, dementia, neuropathic pain and sleep disorders), metabolic syndrome (e.g., obesity) and allergic disorders. Novel chemical series from the most recent 2 years of patent literature have been reviewed. While overall structural diversity is moderate, these represent or relate to some of the compounds progressing through clinical trials (e.g., GSK-189254). However, an H₃ receptor drug still has yet to reach the market. Patenting activity is likely to remain high in the near future, bolstered by the commercial promise of potential H₃ receptor drugs.

Keywords::

• allergy
• CNS disorders
• H₃ antagonist
• H₃ inverse agonist
• H₃ receptor
• histamine
• metabolic syndrome
• obesity

Acknowledgment

The authors would like to thank Robert Aslanian and the reviewers of this manuscript for their valuable comments and suggestions.