Histamine and antihistamines

Histamine is one of the most extensively studied biological amines in medicine. It stimulates smooth muscle contraction and gastric acid secretion, increases vascular permeability, functions as a neurotransmitter, and plays various roles in immunomodulation, inflammation, haematopoiesis and cell proliferation. Moreover, it plays a pivotal role in the pathogenesis of allergic inflammation. Histamine exerts its biological effects through four G-protein-coupled receptors designated H1–H4. H1 and H2 receptors are widely distributed, whereas H3 receptors are mainly presynaptic and H4 receptors are mainly haematopoietic. H1 antihistamines are classified as first-generation and second-generation compounds. First-generation H1 antihistamines lack H1 specificity and cross the blood–brain barrier, causing sedation. Second-generation H1 antihistamines are less sedating and highly H1 selective. First- and second-generation H1 antihistamines have well-documented anti-allergic and anti-inflammatory effects and are well established as first- or second-line treatments for a variety of allergic disorders including allergic rhinitis, urticaria and atopic dermatitis. First-generation drugs are also used in the treatment of vestibular disorders and can be used as sedatives, sleeping aids and anti-emetics. H2 antihistamines are widely used in the treatment of gastric acid-related disorders; however, proton pump inhibitors are becoming the drugs of first choice in some of these disorders. H3 antihistamines are expected to be of potential value in the treatment of narcolepsy, obesity, Parkinson’s disease, depression, Alzheimer’s disease and attention deficit hyperactivity disorder. Moreover, evidence from preclinical trials indicates that H4 antihistamines could be of therapeutic benefit in the management of various immune and inflammatory disorders.