Norastemizole

Norastemizole is a histamine H₁ receptor antagonist (IC₅₀ = 4.1 nM) and an active metabolite of the histamine H₁ receptor antagonist and ether-a-go-go (ERG) channel blocker astemizole (Item No. 16967).^1,2 It is formed from astemizole by the cytochrome P450 (CYP) isoform 3A4 (CYP3A4).² Norastemizole also inhibits currents in a whole-cell patch-clamp assay using HEK293 cells expressing human-ether-a-go-go (hERG), also known as K_v11.1 (IC₅₀ = 27.7 nM).³ It prevents IL-1β-induced increases in the levels of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) when used at a concentration of 100 µM.⁴ Norastemizole (1 mg/kg) inhibits passive cutaneous anaphylaxis induced by ovalbumin (OVA) or the biogenic amine histamine (Item No. 33828), but not by bradykinin, in guinea pigs. It inhibits eosinophil infiltration into the lungs of mice in a mouse model of OVA-induced asthma when administered at a dose of 1 mg/kg.

WARNING This product is not for human or veterinary use.

1. Oppenheimer, J.J., and Casale, T.B. Next generation antihistamines: Therapeutic rationale, accomplishments and advances. Expert Opin. Investig. Drugs 11(6), 807-817 (2002).

2. S., M., and Y., Y. Involvement of multiple human cytochromes P450 in the liver microsomal metabolism of astemizole and a comparison with terfenadine. Br. J. Clin. Pharmacol. 51(2), 133-142 (2001).

3. Zhou, Z., Vorperian, V.R., Gong, Q., et al. Block of HERG potassium channels by the antihistamine astemizole and its metabolites desmethylastemizole and norastemizole. J. Cardiovasc. Electrophysiol. 10(6), 836-843 (1999).

4. Lever, R., Hefni, A., Moffatt, J.D., et al. Effect of tecastemizole on pulmonary and cutaneous allergic inflammatory responses. Clin. Exp. Allergy 37(6), 909-917 (2007).