Tecastemizole, A Major Metabolite of Astemizole, is a Potent and Selective H1 receptor Antagonist

Histamine Receptors are a class of G protein-coupled receptors with histamine as their endogenous ligand. There are four types histamine receptors, H1R, H2R, H3R, and H4R. Histamine receptors play a crucial and significant role in the development of various allergic diseases. Histamine has diverse effects, both pro-inflammatory and anti-inflammatory. And they are determined by both the histamine receptor subtype and the cells stimulated types. The H1-receptor drives cellular migration, nociception, vasodilatation, and bronchoconstriction, whereas the H2-receptor modifies gastric acid secretion, airway mucus production, and vascular permeability. The H3-receptor plays an important role in neuro-inflammatory diseases. The H4-receptor also play an important role in allergy and inflammation.

H1R exsits in many tissues and cells, including nerves, respiratory epithelium, endothelial cells, hepatic cells, vascular smooth muscle cells, dendritic cells, and lymphocytes. Histamine activates H1R through Gαq/11, which then activates phospholipase C and increases intracellular Ca++ levels. Activation via H1R may also enhance both Th1- and Th2-type immune responses. In addition, IL-3 activation can increase H1R expression on Th1 cells, and histamine can enhance B cell proliferation, which is absent in H1R-deficient mice. H1R-antagonists can significantly decrease asthma symptoms and improve pulmonary function in persistent asthma.

Tecastemizole (Norastemizole) is a major metabolite of astemizole. Tecastemizole is a potent and selective H1 receptor antagonist. Evidence suggests that Tecastemizole possess anti-inflammatory effects. Tecastemizole inhibits antigen-induced eosinophil recruitment to the lungs of allergic mice in a dose-dependent manner. Furthermore, combination of a sub-effective dose of Tecastemizole, combined with a sub-effective dose of dexamethasone inhibited eosinophil accumulation in this model. Therefore, Tecastemizole shows great promise as potential next-generation antihistamine allergy medication.

All in all, Tecastemizole, a major metabolite of Astemizole, is a potent and selective H1 receptor antagonist.


[1]. Thangam EB, et, al. 2018 Aug 13;9:1873.

[2]. Thangam EB, et, al. Front Immunol. 2018 Aug 13;9:1873.