The expanding role of H1 antihistamines: a patent survey of selective and dual activity compounds 2005-2010

Expert Opin Ther Pat. 2010 Sep;20(9):1197-218. doi: 10.1517/13543776.2010.510516.


Importance of the field: Histamine plays a key role in physiological processes through its interaction with H(1-4) histamine receptors. The H(1) receptor is a key element in the pathophysiology of allergic responses. H(1) antihistamine use is a key strategy for therapy in allergy.

Areas covered in this review: Several new chemical entities with improved efficacy in allergic disease have been pursued. Addition of multiple antagonist activities in single compounds has been the focus of current research. Involvement of the H(1) receptor in sleep has led to the evaluation of new compounds as sedative hypnotics.

What the reader will gain: In all, 57 patents detail the evolution of new chemical entities. Dual H(1)-CC-chemokine receptor-3 and H(1)-H(3) antagonists have entered the clinic for allergic indications. Efforts to develop H(1) antihistamines as sedative hypnotics have increased, with several compounds entering the clinic. The dual H(1)-5-HT(2A) antagonist doxepin has been approved for sleep disorders while another compound is currently in clinical trials.

Take home message: The development of multiple activity H(1) antihistamines in allergy has met with limited success due in part to a competitive commercial environment. New sedative hypnotics may show potential but will need to demonstrate significant benefits in an increasingly competitive landscape.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Allergic Agents / pharmacology
  • Drug Design*
  • Histamine H1 Antagonists / pharmacology
  • Humans
  • Hypersensitivity / drug therapy*
  • Hypersensitivity / physiopathology
  • Hypnotics and Sedatives / pharmacology
  • Patents as Topic
  • Receptors, Histamine H1 / drug effects*
  • Receptors, Histamine H1 / metabolism
  • Sleep Initiation and Maintenance Disorders / drug therapy
  • Sleep Initiation and Maintenance Disorders / physiopathology


  • Anti-Allergic Agents
  • Histamine H1 Antagonists
  • Hypnotics and Sedatives
  • Receptors, Histamine H1