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

Abstract

Importance of the field: Histamine plays a key role in physiological processes through its interaction with H_{1 – 4} histamine receptors. The H₁ receptor is a key element in the pathophysiology of allergic responses. H₁ 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 H₁ 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 H₁–CC-chemokine receptor-3 and H₁ – H₃ antagonists have entered the clinic for allergic indications. Efforts to develop H₁ antihistamines as sedative hypnotics have increased, with several compounds entering the clinic. The dual H₁–5-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 H₁ 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.

Keywords::

• 5-HT_2A receptor
• allergic disease
• CCR3 receptor
• H₁ antihistamines
• H₁ receptor
• H₃ receptor
• inflammatory disease
• insomnia
• pruritis

Notes

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