Could terfenadine be the new hope for antihistamines?

Antihistamines are very widely used class B drugs in medicine, mainly histamine receptor antagonists, which act on histamine receptors in the body to reduce the effect of histamine, thus reducing the body’s allergic reaction to allergens or reducing the secretion of stomach acid.

H1 receptors are mainly distributed in capillaries, bronchial tubes, and intestinal smooth muscle. When H1 receptors are activated, they can cause allergic urticaria pruritus accompanied by angioneurotic edema, laryngospasm, bronchospasm, etc. H2 receptors are mainly distributed in gastric wall cells and vascular smooth muscle cells and promote gastric acid secretion and capillary dilation. H2 receptors are mainly distributed in gastric lining cells and vascular smooth muscle cells. Histamine H1 receptor antagonist is the most widely used non-specific abnormal anti-allergic drug, which can compete with histamine for H1 receptor on effector cells, so that histamine can not bind to the H1 receptor, thus inhibiting its effect of causing allergic reactions. In the latest medical research, scientists have discovered a new antihistamine: terfenadine. What characteristics of terfenadine make us think it will be the new hope of antihistamine drugs?


What is terfenadine?

Terfenadine is a potent hERG open channel blocker with an IC50 of 204 nM. It is an H1 histamine receptor antagonist that acts as a potent apoptosis inducer in melanoma cells by regulating Ca2+ homeostasis. Terfenadine induces ROS-dependent apoptosis and activates caspase-4,-2,-9. This drug undergoes extensive first-pass hepatic metabolism via the cytochrome P450 enzyme CYP3A4 as its pharmacologically active metabolite, fexofenadine. According to scientists, terfenadine is cardiotoxic and can induce QT interval prolongation by blocking cardiac potassium channels.

Pharmacological effects of terfenadine

Terfenadine acts as a peripherally selective antihistamine or antagonist of the histamine H1 receptor. It is a prodrug that is generally entirely metabolized in the liver by the cytochrome P450 3A4 enzyme to the active form of fexofenadine. Because terfenadine is almost entirely metabolized by the liver immediately after leaving the intestine, terfenadine is usually not measurable in plasma. However, terfenadine is cardiotoxic at higher doses, whereas its primary active metabolite is not. Terfenadine acts as a potassium channel blocker (Kv11.1 encoded by the gene hERG) and has antihistamine effects. Because its active metabolite is not a potassium channel blocker, terfenadine is not cardiotoxic. Toxicity may occur suddenly due to interactions with other drugs (e.g., erythromycin) or foods (e.g., grapefruit), even after years of use without problems. Adding or increasing the dose of these CYP3A4 inhibitors makes it more difficult for the body to metabolize and clear terfenadine. At larger plasma concentrations, this may produce toxic effects on cardiac rhythm (e.g., ventricular tachycardia and tachycardia).

History and Prospect

terfenadine was synthesized by chemists at Richardson-Merrell in 1973 as a potential sedative. However, it also was found to be inactive for this purpose because it could not cross the blood-brain barrier or enter the central nervous system. A pharmacologist named Richard Kinsolving noticed that terfenadine showed structural similarity to the antihistamine Benadryl, so terfenadine was tested as an antihistamine. It was found to be a non-sedating antihistamine and was the first such drug to be discovered.

Benchchem scientists have found through their research that terfenadine also has uses that can prevent sneezing, runny nose, itchy and watery eyes, and other allergy symptoms. In the near future, terfenadine will definitely become a new hope for antihistamine drugs.

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